Publications

@article{nokey_67,

title = {Rfam 15: RNA families database in 2025},

author = {Nancy Ontiveros-Palacios and Emma Cooke and Eric P. Nawrocki and Sandra Triebel and Manja Marz and Elena Rivas and Sam Griffiths-Jones and Anton I. Petrov and Alex Bateman and Blake Sweeney},

doi = {10.1093/nar/gkae1023},

year  = {2025},

date = {2025-01-06},

urldate = {2024-11-11},

journal = {Nucleic Acids Research},

abstract = {The Rfam database, a widely used repository of non-coding RNA families, has undergone significant updates in release 15.0. This paper introduces major improvements, including the expansion of Rfamseq to 26 106 genomes, a 76% increase, incorporating the latest UniProt reference proteomes and additional viral genomes. Sixty-five RNA families were enhanced using experimentally determined 3D structures, improving the accuracy of consensus secondary structures and annotations. R-scape covariation analysis was used to refine structural predictions in 26 families. Gene Ontology (GO) and Sequence Ontology annotations were comprehensively updated, increasing GO term coverage to 75% of families. The release adds 14 new Hepatitis C Virus RNA families and completes microRNA family synchronization with miRBase, resulting in 1603 microRNA families. New data types, including FULL alignments, have been implemented. Integration with APICURON for improved curator attribution and multiple website enhancements further improve user experience. These updates significantly expand Rfam’s coverage and improve annotation quality, reinforcing its critical role in RNA research, genome annotation and the development of machine learning models. Rfam is freely available at https://rfam.org.},

keywords = {database, ncRNAs, RNA structure, RNA-RNA interactions},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Engineering extracellular vesicles to transiently permeabilize the blood–brain barrier},

author = {Francesca Tomatis and Susana Rosa and Susana Simões and Marta Barão and Carlos Jesus and João Novo and Emanuel Barth and Manja Marz and Lino Ferreira},

doi = {10.1186/s12951-024-03019-w},

year  = {2024},

date = {2024-12-02},

journal = {Journal of Nanobiotechnology},

volume = {22},

abstract = {Background

Drug delivery to the brain is challenging due to the restrict permeability of the blood brain barrier (BBB). Recent studies indicate that BBB permeability increases over time during physiological aging likely due to factors (including extracellular vesicles (EVs)) that exist in the bloodstream. Therefore, inspiration can be taken from aging to develop new strategies for the transient opening of the BBB for drug delivery to the brain.

Results

Here, we evaluated the impact of small EVs (sEVs) enriched with microRNAs (miRNAs) overexpressed during aging, with the capacity to interfere transiently with the BBB. Initially, we investigated whether the miRNAs were overexpressed in sEVs collected from plasma of aged individuals. Next, we evaluated the opening properties of the miRNA-enriched sEVs in a static or dynamic (under flow) human in vitro BBB model. Our results showed that miR-383-3p-enriched sEVs significantly increased BBB permeability in a reversible manner by decreasing the expression of claudin 5, an important tight junction protein of brain endothelial cells (BECs) of the BBB, mediated in part by the knockdown of activating transcription factor 4 (ATF4).

Conclusions

Our findings suggest that engineered sEVs have potential as a strategy for the temporary BBB opening, making it easier for drugs to reach the brain when injected into the bloodstream.},

keywords = {aging, extracellular vesicles, ncRNAs},

pubstate = {published},

tppubtype = {article}

}

@article{nokey_66,

title = {RNA-protein interaction prediction without high-throughput data: An overview and benchmark of \textit{in silico} tools},

author = {Sarah Krautwurst and Kevin Lamkiewicz},

doi = {10.1016/j.csbj.2024.11.015},

issn = {2001-0370},

year  = {2024},

date = {2024-11-08},

journal = {Computational and Structural Biotechnology Journal},

volume = {23},

pages = {4036-4046},

abstract = {RNA-protein interactions (RPIs) are crucial for accurately operating various processes in and between organisms across kingdoms of life. Mutual detection of RPI partner molecules depends on distinct sequential, structural, or thermodynamic features, which can be determined via experimental and bioinformatic methods. Still, the underlying molecular mechanisms of many RPIs are poorly understood. It is further hypothesized that many RPIs are not even described yet. Computational RPI prediction is continuously challenged by the lack of data and detailed research of very specific examples. With the discovery of novel RPI complexes in all kingdoms of life, adaptations of existing RPI prediction methods are necessary. Continuously improving computational RPI prediction is key in advancing the understanding of RPIs in detail and supplementing experimental RPI determination. The growing amount of data covering more species and detailed mechanisms support the accuracy of prediction tools, which in turn support specific experimental research on RPIs. Here, we give an overview of RPI prediction tools that do not use high-throughput data as the user's input. We review the tools according to their input, usability, and output. We then apply the tools to known RPI examples across different kingdoms of life. Our comparison shows that the investigated prediction tools do not favor a certain species and equip the user with results varying in degree of information, from an overall RPI score to detailed interacting residues. Furthermore, we provide a guide tree to assist users which RPI prediction tool is appropriate for their available input data and desired output.},

keywords = {ncRNAs, proteins, RNA / transcriptomics, RNA structure},

pubstate = {published},

tppubtype = {article}

}

@article{nokey_62,

title = {Comprehensive survey of conserved RNA secondary structures in full-genome alignment of Hepatitis C virus},

author = {Sandra Triebel and Kevin Lamkiewicz and Nancy Ontiveros and Blake Sweeney and Peter F. Stadler and Anton I. Petrov and Michael Niepmann and Manja Marz},

doi = {10.1038/s41598-024-62897-0},

year  = {2024},

date = {2024-07-02},

urldate = {2024-07-02},

journal = {Scientific Reports},

volume = {14},

issue = {1},

abstract = {Hepatitis C virus (HCV) is a plus-stranded RNA virus that often chronically infects liver hepatocytes and causes liver cirrhosis and cancer. These viruses replicate their genomes employing error-prone replicases. Thereby, they routinely generate a large ‘cloud’ of RNA genomes (quasispecies) which—by trial and error—comprehensively explore the sequence space available for functional RNA genomes that maintain the ability for efficient replication and immune escape. In this context, it is important to identify which RNA secondary structures in the sequence space of the HCV genome are conserved, likely due to functional requirements. Here, we provide the first genome-wide multiple sequence alignment (MSA) with the prediction of RNA secondary structures throughout all representative full-length HCV genomes. We selected 57 representative genomes by clustering all complete HCV genomes from the BV-BRC database based on k-mer distributions and dimension reduction and adding RefSeq sequences. We include annotations of previously recognized features for easy comparison to other studies. Our results indicate that mainly the core coding region, the C-terminal NS5A region, and the NS5B region contain secondary structure elements that are conserved beyond coding sequence requirements, indicating functionality on the RNA level. In contrast, the genome regions in between contain less highly conserved structures. The results provide a complete description of all conserved RNA secondary structures and make clear that functionally important RNA secondary structures are present in certain HCV genome regions but are largely absent from other regions. Full-genome alignments of all branches of Hepacivirus C are provided in the supplement.},

keywords = {evolution, ncRNAs, phylogenetics, RNA structure, RNA-RNA interactions, virus host interaction, viruses},

pubstate = {published},

tppubtype = {article}

}

@article{nokey_42,

title = {PAPAS Suppresses Breast Carcinogenesis by Promoting Differentiation of Mammary Epithelial Cells},

author = {Sijia Ren and Feng Bai and Clara Stanko and Muriel Ritsch and Tino Schenk and Emanuel Barth and Xin-Hai Pei and Holger Bierhoff

},

doi = {10.2139/ssrn.4436847},

year  = {2024},

date = {2024-01-23},

urldate = {2023-05-23},

journal = {Cell Reports},

abstract = {Extensive remodeling of the female mammary epithelium during development and pregnancy has been linked to cancer susceptibility. The faithful response of mammary epithelial cells (MECs) to hormone signaling is key to avoid breast cancer development. Here we show that lactogenic differentiation of murine MECs requires epigenetic silencing of genes encoding ribosomal RNA (rRNA) by the antisense transcript PAPAS. Accordingly, knockdown of PAPAS derepresses rRNA genes, attenuates the response to lactogenic hormones, and induces malignant transformation. Restoring PAPAS levels in breast cancer cells reduces tumorigenicity and, as revealed by transcriptomics, immune evasion potential. Mechanistically, we show that PAPAS transcription depends on R-loop formation at the 3’ end of rRNA genes, which is repressed by RNase H1 and replication protein A (RPA) overexpression in breast cancer cells. Depletion of PAPAS, and upregulation of RNase H1 and RPA in human breast cancer underpin the clinical relevance of our findings.},

keywords = {cancer, ncRNAs, RNA structure},

pubstate = {published},

tppubtype = {article}

}

@article{nokey_49,

title = {Decoding cell-type contributions to the cfRNA transcriptomic landscape of liver cancer},

author = {Aram Safrastyan and Christian {Höner Zu Siederdissen} and Damian Wollny},

doi = {10.1186/s40246-023-00537-w},

year  = {2023},

date = {2023-10-05},

journal = {Hum Genomics},

volume = {17},

issue = {1},

pages = {90},

abstract = {Background

Liquid biopsy, particularly cell-free RNA (cfRNA), has emerged as a promising non-invasive diagnostic tool for various diseases, including cancer, due to its accessibility and the wealth of information it provides. A key area of interest is the composition and cellular origin of cfRNA in the blood and the alterations in the cfRNA transcriptomic landscape during carcinogenesis. Investigating these changes can offer insights into the manifestations of tissue alterations in the blood, potentially leading to more effective diagnostic strategies. However, the consistency of these findings across different studies and their clinical utility remains to be fully elucidated, highlighting the need for further research in this area.



Results

In this study, we analyzed over 350 blood samples from four distinct studies, investigating the cell type contributions to the cfRNA transcriptomic landscape in liver cancer. We found that an increase in hepatocyte proportions in the blood is a consistent feature across most studies and can be effectively utilized for classifying cancer and healthy samples. Moreover, our analysis revealed that in addition to hepatocytes, liver endothelial cell signatures are also prominent in the observed changes. By comparing the classification performance of cellular proportions to established markers, we demonstrated that cellular proportions could distinguish cancer from healthy samples as effectively as existing markers and can even enhance classification when used in combination with these markers.



Conclusions

Our comprehensive analysis of liver cell-type composition changes in blood revealed robust effects that help classify cancer from healthy samples. This is especially noteworthy, considering the heterogeneous nature of datasets and the etiological distinctions of samples. Furthermore, the observed differences in results across studies underscore the importance of integrative and comparative approaches in the future research to determine the consistency and robustness of findings. This study contributes to the understanding of cfRNA composition in liver cancer and highlights the potential of cellular deconvolution in liquid biopsy.},

keywords = {cancer, ncRNAs},

pubstate = {published},

tppubtype = {article}

}

@article{nokey_46,

title = {RNA-based sensitive fungal pathogen detection},

author = {Julia Micheel and Franziska Aron and Abdulrahman A. Kelani and Christian Girbardt and Matthew G. Blango and Grit Walther and Damian Wollny},

doi = {10.1101/2023.09.26.559494},

year  = {2023},

date = {2023-09-26},

urldate = {2023-09-26},

journal = {bioRxiv},

abstract = {Detecting fungal pathogens, a major cause of severe systemic infections, remains challenging due to the difficulty and time-consuming nature of diagnostic methods. This delay in identification hinders targeted treatment decisions and may lead to unnecessary use of broad-spectrum antibiotics. To expedite treatment initiation, one promising approach is to directly detect pathogen nucleic acids such as DNA, which is often preferred to RNA because of its inherent stability. However, a higher number of RNA molecules per cell makes RNA a more promising diagnostic target which is particularly prominent for highly expressed genes such as rRNA. Here, we investigated the utility of a minimal input-specialized reverse transcription protocol to increase diagnostic sensitivity. This proof-of-concept study demonstrates that fungal rRNA detection by the minimal input protocol is drastically more sensitive compared to detection of genomic DNA even with high levels of human RNA background. This approach can detect several of the most relevant human pathogenic fungal genera, such as Aspergillus, Candida, and Fusarium and thus represents a powerful, cheap, and easily adaptable addition to currently available diagnostic assays.},

keywords = {fungi, ncRNAs, RNA / transcriptomics},

pubstate = {published},

tppubtype = {article}

}

@article{nokey_48,

title = {Detection of reproducible liver cancer specific ligand-receptor signaling in blood},

author = {Aram Safrastyan and Damian Wollny},

doi = {10.1101/2023.09.25.559274},

year  = {2023},

date = {2023-09-25},

urldate = {2023-09-25},

journal = {bioRxiv},

abstract = {Cell-cell communication mediated by ligand-receptor interactions (LRI) is critical to coordinating diverse biological processes in homeostasis and disease. Lately, our understanding of these processes has greatly expanded through the inference of cellular communication, utilizing RNA extracted from bulk tissue or individual cells. Considering the challenge of obtaining tissue biopsies for these approaches, we considered the potential of studying cell-free RNA obtained from blood. To test the feasibility of this approach, we used the BulkSignalR algorithm across 295 cell-free RNA samples and compared the LRI profiles across multiple cancer types and healthy donors. Interestingly, we detected specific and reproducible LRIs particularly in the blood of liver cancer patients compared to healthy donors. We found an increase in the magnitude of hepatocyte interactions, notably hepatocyte autocrine interactions in liver cancer patients. Additionally, a robust panel of 30 liver cancer-specific LRIs presents a bridge linking liver cancer pathogenesis to discernible blood markers. In summary, our approach shows the plausibility of detecting liver LRIs in blood and builds upon the biological understanding of cell-free transcriptomes.},

keywords = {cancer, ncRNAs},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Identification of altered miRNAs and their targets in placenta accreta},

author = {José M Murrieta-Coxca and Emanuel Barth and Paulina Fuentes-Zacarias and Ruby N Gutiérrez-Samudio and Tanja Groten and Alexandra Gellhaus and Angela Köninger and Manja Marz and Udo R Markert and Diana M Morales-Prieto

},

doi = {10.3389/fendo.2023.1021640},

year  = {2023},

date = {2023-03-03},

journal = {Front Endocrinol},

volume = {14},

pages = {1021640},

abstract = {Placenta accreta spectrum (PAS) is one of the major causes of maternal morbidity and mortality worldwide with increasing incidence. PAS refers to a group of pathological conditions ranging from the abnormal attachment of the placenta to the uterus wall to its perforation and, in extreme cases, invasion into surrounding organs. Among them, placenta accreta is characterized by a direct adhesion of the villi to the myometrium without invasion and remains the most common diagnosis of PAS. Here, we identify the potential regulatory miRNA and target networks contributing to placenta accreta development. Using small RNA-Seq followed by RT-PCR confirmation, altered miRNA expression, including that of members of placenta-specific miRNA clusters (e.g., C19MC and C14MC), was identified in placenta accreta samples compared to normal placental tissues. In situ hybridization (ISH) revealed expression of altered miRNAs mostly in trophoblast but also in endothelial cells and this profile was similar among all evaluated degrees of PAS. Kyoto encyclopedia of genes and genomes (KEGG) analyses showed enriched pathways dysregulated in PAS associated with cell cycle regulation, inflammation, and invasion. mRNAs of genes associated with cell cycle and inflammation were downregulated in PAS. At the protein level, NF-κB was upregulated while PTEN was downregulated in placenta accreta tissue. The identified miRNAs and their targets are associated with signaling pathways relevant to controlling trophoblast function. Therefore, this study provides miRNA:mRNA associations that could be useful for understanding PAS onset and progression.},

keywords = {ncRNAs, pregnancy, RNA / transcriptomics},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {The Role of Non-Coding RNAs in the Human Placenta},

author = {Milena Žarković and Franziska Hufsky and Udo R Markert and Manja Marz},

doi = {10.3390/cells11091588},

year  = {2022},

date = {2022-05-09},

journal = {Cells},

volume = {11},

issue = {9},

pages = {1588},

abstract = {Non-coding RNAs (ncRNAs) play a central and regulatory role in almost all cells, organs, and species, which has been broadly recognized since the human ENCODE project and several other genome projects. Nevertheless, a small fraction of ncRNAs have been identified, and in the placenta they have been investigated very marginally. To date, most examples of ncRNAs which have been identified to be specific for fetal tissues, including placenta, are members of the group of microRNAs (miRNAs). Due to their quantity, it can be expected that the fairly larger group of other ncRNAs exerts far stronger effects than miRNAs. The syncytiotrophoblast of fetal origin forms the interface between fetus and mother, and releases permanently extracellular vesicles (EVs) into the maternal circulation which contain fetal proteins and RNA, including ncRNA, for communication with neighboring and distant maternal cells. Disorders of ncRNA in placental tissue, especially in trophoblast cells, and in EVs seem to be involved in pregnancy disorders, potentially as a cause or consequence. This review summarizes the current knowledge on placental ncRNA, their transport in EVs, and their involvement and pregnancy pathologies, as well as their potential for novel diagnostic tools.},

keywords = {extracellular vesicles, ncRNAs, pregnancy, RNA / transcriptomics},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Advances in Non-Coding RNA Sequencing},

author = {Julia Micheel and Aram Safrastyan and Damian Wollny

},

doi = {10.3390/ncrna7040070},

year  = {2021},

date = {2021-10-30},

journal = {Noncoding RNA},

volume = {7},

number = {4},

pages = {70},

abstract = {Non-coding RNAs (ncRNAs) comprise a set of abundant and functionally diverse RNA molecules. Since the discovery of the first ncRNA in the 1960s, ncRNAs have been shown to be involved in nearly all steps of the central dogma of molecular biology. In recent years, the pace of discovery of novel ncRNAs and their cellular roles has been greatly accelerated by high-throughput sequencing. Advances in sequencing technology, library preparation protocols as well as computational biology helped to greatly expand our knowledge of which ncRNAs exist throughout the kingdoms of life. Moreover, RNA sequencing revealed crucial roles of many ncRNAs in human health and disease. In this review, we discuss the most recent methodological advancements in the rapidly evolving field of high-throughput sequencing and how it has greatly expanded our understanding of ncRNA biology across a large number of different organisms.},

keywords = {ncRNAs, RNA / transcriptomics},

pubstate = {published},

tppubtype = {article}

}

@article{Kalvari:21,

title = {Rfam 14: expanded coverage of metagenomic, viral and microRNA families},

author = {Ioanna Kalvari and Eric P Nawrocki and Nancy Ontiveros-Palacios and Joanna Argasinska and Kevin Lamkiewicz and Manja Marz and Sam Griffiths-Jones and Claire Toffano-Nioche and Daniel Gautheret and Zasha Weinberg and Elena Rivas and Sean R Eddy and Robert D Finn and Alex Bateman and Anton I Petrov},

url = {https://rfam.org/},

doi = {10.1093/nar/gkaa1047},

year  = {2020},

date = {2020-11-19},

urldate = {2020-11-19},

journal = {Nucleic Acids Res},

volume = {49},

number = {D1},

pages = {D192--D200},

publisher = {Oxford University Press (OUP)},

abstract = {Rfam is a database of RNA families where each of the 3444 families is represented by a multiple sequence alignment of known RNA sequences and a covariance model that can be used to search for additional members of the family. Recent developments have involved expert collaborations to improve the quality and coverage of Rfam data, focusing on microRNAs, viral and bacterial RNAs. We have completed the first phase of synchronising microRNA families in Rfam and miRBase, creating 356 new Rfam families and updating 40. We established a procedure for comprehensive annotation of viral RNA families starting with Flavivirus and Coronaviridae RNAs. We have also increased the coverage of bacterial and metagenome-based RNA families from the ZWD database. These developments have enabled a significant growth of the database, with the addition of 759 new families in Rfam 14. To facilitate further community contribution to Rfam, expert users are now able to build and submit new families using the newly developed Rfam Cloud family curation system. New Rfam website features include a new sequence similarity search powered by RNAcentral, as well as search and visualisation of families with pseudoknots. Rfam is freely available at https://rfam.org.},

keywords = {alignment, annotation, bacteria, coronavirus, database, metagenomics, ncRNAs, RNA / transcriptomics, software, viruses},

pubstate = {published},

tppubtype = {article}

}

@article{Gerresheim:20,

title = {Ribosome Pausing at Inefficient Codons at the End of the Replicase Coding Region Is Important for Hepatitis C Virus Genome Replication},

author = {Gesche K. Gerresheim and Carolin S. Hess and Lyudmila A. Shalamova and Markus Fricke and Manja Marz and Dmitri E. Andreev and Ivan N. Shatsky and Michael Niepmann},

doi = {10.3390/ijms21186955},

year  = {2020},

date = {2020-09-22},

urldate = {2020-09-22},

journal = {Int J Mol Sci},

volume = {21},

number = {18},

pages = {6955},

publisher = {MDPI AG},

abstract = {Hepatitis C virus (HCV) infects liver cells and often causes chronic infection, also leading to liver cirrhosis and cancer. In the cytoplasm, the viral structural and non-structural (NS) proteins are directly translated from the plus strand HCV RNA genome. The viral proteins NS3 to NS5B proteins constitute the replication complex that is required for RNA genome replication via a minus strand antigenome. The most C-terminal protein in the genome is the NS5B replicase, which needs to initiate antigenome RNA synthesis at the very 3′-end of the plus strand. Using ribosome profiling of cells replicating full-length infectious HCV genomes, we uncovered that ribosomes accumulate at the HCV stop codon and about 30 nucleotides upstream of it. This pausing is due to the presence of conserved rare, inefficient Wobble codons upstream of the termination site. Synonymous substitution of these inefficient codons to efficient codons has negative consequences for viral RNA replication but not for viral protein synthesis. This pausing may allow the enzymatically active replicase core to find its genuine RNA template in cis, while the protein is still held in place by being stuck with its C-terminus in the exit tunnel of the paused ribosome.

},

keywords = {cancer, liver, ncRNAs, RNA structure, viruses},

pubstate = {published},

tppubtype = {article}

}

@article{Mostajo:20,

title = {A comprehensive annotation and differential expression analysis of short and long non-coding RNAs in 16 bat genomes},

author = {Nelly F. Mostajo and Marie Lataretu and Sebastian Krautwurst and Florian Mock and Daniel Desirò and Kevin Lamkiewicz and Maximilian Collatz and Andreas Schoen and Friedemann Weber and Manja Marz and Martin Hölzer},

url = {https://www.rna.uni-jena.de/supplements/bats/index.html},

doi = {10.1093/nargab/lqz006},

year  = {2019},

date = {2019-09-30},

urldate = {2019-09-30},

journal = {NAR Genomics Bioinf},

volume = {2},

number = {1},

pages = {lqz006},

abstract = {Although bats are increasingly becoming the focus of scientific studies due to their unique properties, these exceptional animals are still among the least studied mammals. Assembly quality and completeness of bat genomes vary a lot and especially non-coding RNA (ncRNA) annotations are incomplete or simply missing. Accordingly, standard bioinformatics pipelines for gene expression analysis often ignore ncRNAs such as microRNAs or long antisense RNAs. The main cause of this problem is the use of incomplete genome annotations. We present a complete screening for ncRNAs within 16 bat genomes. NcRNAs affect a remarkable variety of vital biological functions, including gene expression regulation, RNA processing, RNA interference and, as recently described, regulatory processes in viral infections. Within all investigated bat assemblies, we annotated 667 ncRNA families including 162 snoRNAs and 193 miRNAs as well as rRNAs, tRNAs, several snRNAs and lncRNAs, and other structural ncRNA elements. We validated our ncRNA candidates by six RNA-Seq data sets and show significant expression patterns that have never been described before in a bat species on such a large scale. Our annotations will be usable as a resource (rna.uni-jena.de/supplements/bats) for deeper studying of bat evolution, ncRNAs repertoire, gene expression and regulation, ecology and important host–virus interactions.},

keywords = {annotation, assembly, differential expression analysis, evolution, ncRNAs, RNA / transcriptomics, virus host interaction, viruses},

pubstate = {published},

tppubtype = {article}

}

@article{Morales-Prieto:19,

title = {Identification of miRNAs and associated pathways regulated by Leukemia Inhibitory Factor in trophoblastic cell lines.},

author = {Diana M. Morales-Prieto and Emanuel Barth and Jose Martín Murrieta-Coxca and Rodolfo R. Favaro and Ruby N. Gutiérrez-Samudio and Wittaya Chaiwangyen and Stephanie Ospina-Prieto and Bernd Gruhn and Ekkehard Schleußner and Manja Marz and Udo R. Markert},

doi = {10.1016/j.placenta.2019.09.005},

year  = {2019},

date = {2019-09-12},

urldate = {2019-09-12},

journal = {Placenta},

volume = {88},

pages = {20--27},

abstract = {Leukemia Inhibitory Factor (LIF) regulates behavior of trophoblast cells and their interaction with immune and endothelial cells. In vitro, trophoblast cell response to LIF may vary depending on the cell model. Reported differences in the miRNA profile of trophoblastic cells may be responsible for these observations. Therefore, miRNA expression was investigated in four trophoblastic cell lines under LIF stimulation followed by in silico analysis of altered miRNAs and their associated pathways. Low density TaqMan miRNA assays were used to quantify levels of 762 mature miRNAs under LIF stimulation in three choriocarcinoma-derived (JEG-3, ACH-3P and AC1-M59) and a trophoblast immortalized (HTR-8/SVneo) cell lines. Expression of selected miRNAs was confirmed in primary trophoblast cells and cell lines by qPCR. Targets and associated pathways of the differentially expressed miRNAs were inferred from the miRTarBase followed by a KEGG Pathway Enrichment Analysis. HTR-8/SVneo and JEG-3 cells were transfected with miR-21-mimics and expression of miR-21 targets was assessed by qPCR. A similar number of miRNAs changed in each tested cell line upon LIF stimulation, however, low coincidence of individual miRNA species was observed and occurred more often among choriocarcinoma-derived cells (complete data set at http://www.ncbi.nlm.nih.gov/geo/ under GEO accession number GSE130489). Altered miRNAs were categorized into pathways involved in human diseases, cellular processes and signal transduction. Six cascades were identified as significantly enriched, including JAK/STAT and TGFB-SMAD. Upregulation of miR-21-3p was validated in all cell lines and primary cells and STAT3 was confirmed as its target. Dissimilar miRNA responses may be involved in differences of LIF effects on trophoblastic cell lines.},

keywords = {differential expression analysis, ncRNAs, pregnancy},

pubstate = {published},

tppubtype = {article}

}

@article{Morales-Prieto:18a,

title = {Peripheral blood exosomes pass blood-brain-barrier and induce glial cell activation},

author = {Diana M. Morales-Prieto and Milan Stojiljkovic and Celia Diezel and Priska-Elisabeth Streicher and Franziska Roestel and Julia Lindner and Sebastian Weis and Christian Schmeer and Manja Marz},

doi = {10.1101/471409},

year  = {2018},

date = {2018-11-29},

urldate = {2018-11-29},

journal = {bioRxiv},

pages = {471409},

publisher = {Cold Spring Harbor Laboratory},

abstract = {Background Exosomes are involved in intracellular communication and contain proteins, mRNAs, miRNAs, and signaling molecules. Exosomes were shown to act as neuroinflammatory mediators involved in neurodegenerative diseases including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS). Brain aging has been associated to increased neuroinflammation. In addition, a decreased extracellular vesicle concentration was observed in aging tissues. The specific mechanisms how exosomes and aging are connected are not known yet.



Results Here we have shown that peripheral injection had almost no effect on selected gene expression in the liver. However, exosome injection has led to changes in the specific markers of glial cell activation (CD68, Iba1, GFAP). Interestingly, only injection of exosomes isolated from aged mice induced significant activation of astrocyte cells, as shown by increased GFAP expression.



Conclusion Transcription levels of genes GFAP, TGF-β, CD68, Iba1 known to be involved in glial cell function are significantly changing after introduction of peripheral extracellular vesicles. Exosomes were able to pass blood brain barrier and induce glial cell activation. GFAP known to be a specific astrocyte activation marker was significantly higher expressed after injection of old but not young exosomes, indicating a possible role of exosomes in the mechanisms of brain aging.},

keywords = {aging, extracellular vesicles, liver, ncRNAs},

pubstate = {published},

tppubtype = {article}

}

@article{Lamkiewicz:18,

title = {Identification of potential microRNAs associated with Herpesvirus family based on bioinformatic analysis},

author = {Kevin Lamkiewicz and Emanuel Barth and Manja Marz and Bashar Ibrahim},

doi = {10.1101/417782},

year  = {2018},

date = {2018-11-09},

urldate = {2018-11-09},

journal = {bioRxiv},

pages = {417782},

publisher = {Cold Spring Harbor Laboratory},

abstract = {MicroRNAs (miRNAs) are known key regulators of gene expression on posttranscriptional level in many organisms encoded in mammals, plants and also several viral families. To date, no homologous gene of a virus-originated miRNA is known in other organisms. To date, only a few homologous miRNA between two different viruses are known, however, no gene of a virus-originated miRNA is known in any organism of other kingdoms. This can be attributed to the fact that classical miRNA detection approaches such as homology-based predictions fail at viruses due to their highly diverse genomes and their high mutation rate.



Here, we applied the virus-derived precursor miRNA (pre-miRNA) prediction pipeline ViMiFi, which combines information about sequence conservation and machine learning-based approaches, on Human Herpesvirus 7 (HHV7) and Epstein-Barr virus (EBV). ViMiFi was able to predict 61 candidates in EBV, which has 25 known pre-miRNAs. From these 25, ViMiFi identified 20. It was further able to predict 18 candidates in the HHV7 genome, in which no miRNA had been described yet. We also studied the undescribed candidates of both viruses for potential functions and found similarities with human snRNAs and miRNAs from mammals and plants.},

keywords = {machine learning, ncRNAs, RNA / transcriptomics, viruses},

pubstate = {published},

tppubtype = {article}

}

@article{Baumgart:17,

title = {A miRNA catalogue and ncRNA annotation of the short-living fish \textit{Nothobranchius furzeri}},

author = {Mario Baumgart and Emanuel Barth and Aurora Savino and Marco Groth and Philipp Koch and Andreas Petzold and Ivan Arisi and Matthias Platzer and Manja Marz and Alessandro Cellerino},

doi = {10.1186/s12864-017-3951-8},

year  = {2017},

date = {2017-09-05},

urldate = {2017-01-01},

journal = {BMC Genomics},

volume = {18},

pages = {693},

abstract = {The short-lived fish Nothobranchius furzeri is the shortest-lived vertebrate that can be cultured in captivity and was recently established as a model organism for aging research. Small non-coding RNAs, especially miRNAs, are implicated in age dependent control of gene expression. Here, we present a comprehensive catalogue of miRNAs and several other non-coding RNA classes (ncRNAs) for Nothobranchius furzeri. Analyzing multiple small RNA-Seq libraries, we show most of these identified miRNAs are expressed in at least one of seven Nothobranchius species. Additionally, duplication and clustering of N. furzeri miRNAs was analyzed and compared to the four fish species Danio rerio, Oryzias latipes, Gasterosteus aculeatus and Takifugu rubripes. A peculiar characteristic of N. furzeri, as compared to other teleosts, was a duplication of the miR-29 cluster. The completeness of the catalogue we provide is comparable to that of the zebrafish. This catalogue represents a basis to investigate the role of miRNAs in aging and development in this species.},

keywords = {aging, annotation, ncRNAs, RNA / transcriptomics},

pubstate = {published},

tppubtype = {article}

}

@article{Riege:17,

title = {Massive Effect on LncRNAs in Human Monocytes During Fungal and Bacterial Infections and in Response to Vitamins A and D},

author = {Konstantin Riege and Martin Hölzer and Tilman E Klassert and Emanuel Barth and Julia Bräuer and Maximilian Collatz and Franziska Hufsky and Nelly F. Mostajo and Magdalena Stock and Bertram Vogel and Hortense Slevogt and Manja Marz},

doi = {10.1038/srep40598},

year  = {2017},

date = {2017-01-17},

urldate = {2017-01-17},

journal = {Sci Rep},

volume = {7},

pages = {40598},

abstract = {Mycoses induced by C.albicans or A.fumigatus can cause important host damage either by deficient or exaggerated immune response. Regulation of chemokine and cytokine signaling plays a crucial role for an adequate inflammation, which can be modulated by vitamins A and D. Non-coding RNAs (ncRNAs) as transcription factors or cis-acting antisense RNAs are known to be involved in gene regulation. However, the processes during fungal infections and treatment with vitamins in terms of therapeutic impact are unknown. We show that in monocytes both vitamins regulate ncRNAs involved in amino acid metabolism and immune system processes using comprehensive RNA-Seq analyses. Compared to protein-coding genes, fungi and bacteria induced an expression change in relatively few ncRNAs, but with massive fold changes of up to 4000. We defined the landscape of long-ncRNAs (lncRNAs) in response to pathogens and observed variation in the isoforms composition for several lncRNA following infection and vitamin treatment. Most of the involved antisense RNAs are regulated and positively correlated with their sense protein-coding genes. We investigated lncRNAs with stimulus specific immunomodulatory activity as potential marker genes: LINC00595, SBF2-AS1 (A.fumigatus) and RP11-588G21.2, RP11-394l13.1 (C.albicans) might be detectable in the early phase of infection and serve as therapeutic targets in the future.},

keywords = {bacteria, differential expression analysis, fungi, ncRNAs, RNA / transcriptomics},

pubstate = {published},

tppubtype = {article}

}

@article{Chaiwangyen:17,

title = {KL 5 Trophoblast-immune cell communication via microRNA transported in extracellular vesicles},

author = {Wittaya Chaiwangyen and Ruby N. Gutiérrez-Samudio and Udo R. Markert and Manja Marz and Diana M. Morales-Prieto and Stephanie Ospina-Prieto},

year  = {2017},

date = {2017-01-01},

urldate = {2017-01-01},

journal = {Pregnancy Hypertens},

volume = {9},

pages = {5},

publisher = {Elsevier},

keywords = {ncRNAs, pregnancy},

pubstate = {published},

tppubtype = {article}

}

@article{Hoelzer:16,

title = {Differential transcriptional responses to Ebola and Marburg virus infection in bat and human cells},

author = {Martin Hölzer and Verena Krähling and Fabian Amman and Emanuel Barth and Stephan H. Bernhart and Victor A. O. Carmelo and Maximilian Collatz and Gero Doose and Florian Eggenhofer and Jan Ewald and Jörg Fallmann and Lasse M. Feldhahn and Markus Fricke and Juliane Gebauer and Andreas J. Gruber and Franziska Hufsky and Henrike Indrischek and Sabina Kanton and Jörg Linde and Nelly F. Mostajo and Roman Ochsenreiter and Konstantin Riege and Lorena Rivarola-Duarte and Abdullah H. Sahyoun and Sita J. Saunders and Stefan E. Seemann and Andrea Tanzer and Bertram Vogel and Stefanie Wehner and Michael T. Wolfinger and Rolf Backofen and Jan Gorodkin and Ivo Grosse and Ivo Hofacker and Steve Hoffmann and Christoph Kaleta and Peter F. Stadler and Stephan Becker and Manja Marz},

doi = {10.1038/srep34589},

year  = {2016},

date = {2016-10-07},

urldate = {2016-10-07},

journal = {Sci Rep},

volume = {6},

pages = {34589},

abstract = {The unprecedented outbreak of Ebola in West Africa resulted in over 28,000 cases and 11,000 deaths, underlining the need for a better understanding of the biology of this highly pathogenic virus to develop specific counter strategies. Two filoviruses, the Ebola and Marburg viruses, result in a severe and often fatal infection in humans. However, bats are natural hosts and survive filovirus infections without obvious symptoms. The molecular basis of this striking difference in the response to filovirus infections is not well understood. We report a systematic overview of differentially expressed genes, activity motifs and pathways in human and bat cells infected with the Ebola and Marburg viruses, and we demonstrate that the replication of filoviruses is more rapid in human cells than in bat cells. We also found that the most strongly regulated genes upon filovirus infection are chemokine ligands and transcription factors. We observed a strong induction of the JAK/STAT pathway, of several genes encoding inhibitors of MAP kinases (DUSP genes) and of PPP1R15A, which is involved in ER stress-induced cell death. We used comparative transcriptomics to provide a data resource that can be used to identify cellular responses that might allow bats to survive filovirus infections.},

keywords = {differential expression analysis, ncRNAs, RNA / transcriptomics, virus host interaction, viruses},

pubstate = {published},

tppubtype = {article}

}

@article{Gerresheim:17,

title = {microRNA-122 target sites in the hepatitis C virus RNA NS5B coding region and 3' untranslated region: function in replication and influence of RNA secondary structure},

author = {Gesche K Gerresheim and Nadia Dünnes and Anika Nieder-Röhrmann and Lyudmila A Shalamova and Markus Fricke and Ivo Hofacker and Christian {Höner zu Siederdissen} and Manja Marz and Michael Niepmann},

doi = {10.1007/s00018-016-2377-9},

year  = {2016},

date = {2016-09-27},

urldate = {2016-09-27},

journal = {Cell Mol Life Sci},

volume = {74},

pages = {747--760},

abstract = {We have analyzed the binding of the liver-specific microRNA-122 (miR-122) to three conserved target sites of hepatitis C virus (HCV) RNA, two in the non-structural protein 5B (NS5B) coding region and one in the 3' untranslated region (3'UTR). miR-122 binding efficiency strongly depends on target site accessibility under conditions when the range of flanking sequences available for the formation of local RNA secondary structures changes. Our results indicate that the particular sequence feature that contributes most to the correlation between target site accessibility and binding strength varies between different target sites. This suggests that the dynamics of miRNA/Ago2 binding not only depends on the target site itself but also on flanking sequence context to a considerable extent, in particular in a small viral genome in which strong selection constraints act on coding sequence and overlapping cis-signals and model the accessibility of cis-signals. In full-length genomes, single and combination mutations in the miR-122 target sites reveal that site 5B.2 is positively involved in regulating overall genome replication efficiency, whereas mutation of site 5B.3 showed a weaker effect. Mutation of the 3'UTR site and double or triple mutants showed no significant overall effect on genome replication, whereas in a translation reporter RNA, the 3'UTR target site inhibits translation directed by the HCV 5'UTR. Thus, the miR-122 target sites in the 3'-region of the HCV genome are involved in a complex interplay in regulating different steps of the HCV replication cycle.},

keywords = {liver, ncRNAs, RNA / transcriptomics, RNA structure, viruses},

pubstate = {published},

tppubtype = {article}

}

@article{Marz:15,

title = {MicroRNAs as biomarker of Parkinson disease? Small but mighty},

author = {Manja Marz and Manuela Ferracin and Christine Klein},

doi = {10.1212/WNL.0000000000001275},

year  = {2015},

date = {2015-01-16},

urldate = {2015-01-01},

journal = {Neurology},

volume = {84},

pages = {636--638},

abstract = {Although first described in 1993,1 microRNAs (miRNAs) have only recently emerged as important regulators of gene expression in the context of Parkinson disease (PD).2 miRNAs belong to the class of small non–protein coding RNAs, which mediate the posttranscriptional gene silencing of target RNA transcripts. Specifically, miRNAs are 18- to 25-nucleotide single-stranded RNA, which can inhibit gene expression by binding to the 3′ untranslated region of target genes (figure, A). Of note, the miRNA machinery has a critical role in the biology of dopamine neurons, the predominant cell type affected by neurodegeneration in PD. When eliminating mature miRNAs by deleting Dicer, the ribonuclease required for the early steps of miRNA biogenesis (figure), a nearly complete loss of the dopaminergic neuronal phenotype is observed in a murine cellular model.3 Several subsequent studies addressed the role of miRNAs in PD pathogenesis by focusing on known PD genes and gene products, such as α-synuclein or LRRK2, and identified miRNAs specifically regulating the expression of these proteins.4,5},

keywords = {aging, ncRNAs},

pubstate = {published},

tppubtype = {article}

}

@article{Wehner:14,

title = {Dissemination of 6S RNA among bacteria},

author = {Stefanie Wehner and Katrin Damm and Roland K Hartmann and Manja Marz},

doi = {10.4161/rna.29894},

year  = {2014},

date = {2014-10-31},

urldate = {2014-10-31},

journal = {RNA Biol},

volume = {11},

pages = {1467--1478},

abstract = {6S RNA is a highly abundant small non-coding RNA widely spread among diverse bacterial groups. By competing with DNA promoters for binding to RNA polymerase (RNAP), the RNA regulates transcription on a global scale. RNAP produces small product RNAs derived from 6S RNA as template, which rearranges the 6S RNA structure leading to dissociation of 6S RNA:RNAP complexes. Although 6S RNA has been experimentally analysed in detail for some species, such as Escherichia coli and Bacillus subtilis, and was computationally predicted in many diverse bacteria, a complete and up-to-date overview of the distribution among all bacteria is missing. In this study we searched with new methods for 6S RNA genes in all currently available bacterial genomes. We ended up with a set of 1,750 6S RNA genes, of which 1,367 are novel and bona fide, distributed among 1,610 bacteria, and had a few tentative candidates among the remaining 510 assembled bacterial genomes accessible. We were able to confirm two tentative candidates by Northern blot analysis. We extended 6S RNA genes of the Flavobacteriia significantly in length compared to the present Rfam entry. We describe multiple homologs of 6S RNAs (including split 6S RNA genes) and performed a detailed synteny analysis.},

keywords = {assembly, bacteria, ncRNAs, RNA / transcriptomics, RNA structure},

pubstate = {published},

tppubtype = {article}

}

@article{Wehner:14a,

title = {Detection of very long antisense transcripts by whole transcriptome RNA-Seq analysis of \textit{Listeria monocytogenes} by semiconductor sequencing technology},

author = {Stefanie Wehner and Gopala K Mannala and Xiaoxing Qing and Ramakanth Madhugiri and Trinad Chakraborty and Mobarak A Mraheil and Torsten Hain and Manja Marz},

doi = {10.1371/journal.pone.0108639},

year  = {2014},

date = {2014-10-06},

urldate = {2014-01-01},

journal = {PLoS One},

volume = {9},

pages = {e108639},

abstract = {The Gram-positive bacterium Listeria monocytogenes is the causative agent of listeriosis, a severe food-borne infection characterised by abortion, septicaemia, or meningoencephalitis. L. monocytogenes causes outbreaks of febrile gastroenteritis and accounts for community-acquired bacterial meningitis in humans. Listeriosis has one of the highest mortality rates (up to 30%) of all food-borne infections. This human pathogenic bacterium is an important model organism for biomedical research to investigate cell-mediated immunity. L. monocytogenes is also one of the best characterised bacterial systems for the molecular analysis of intracellular parasitism. Recently several transcriptomic studies have also made the ubiquitous distributed bacterium as a model to understand mechanisms of gene regulation from the environment to the infected host on the level of mRNA and non-coding RNAs (ncRNAs). We have used semiconductor sequencing technology for RNA-seq to investigate the repertoire of listerial ncRNAs under extra- and intracellular growth conditions. Furthermore, we applied a new bioinformatic analysis pipeline for detection, comparative genomics and structural conservation to identify ncRNAs. With this work, in total, 741 ncRNA locations of potential ncRNA candidates are now known for L. monocytogenes, of which 611 ncRNA candidates were identified by RNA-seq. 441 transcribed ncRNAs have never been described before. Among these, we identified novel long non-coding antisense RNAs with a length of up to 5,400 nt e.g. opposite to genes coding for internalins, methylases or a high-affinity potassium uptake system, namely the kdpABC operon, which were confirmed by qRT-PCR analysis. RNA-seq, comparative genomics and structural conservation of L. monocytogenes ncRNAs illustrate that this human pathogen uses a large number and repertoire of ncRNA including novel long antisense RNAs, which could be important for intracellular survival within the infected eukaryotic host.},

keywords = {bacteria, ncRNAs, RNA / transcriptomics},

pubstate = {published},

tppubtype = {article}

}

@article{Lechner:14,

title = {Genomewide comparison and novel ncRNAs of Aquificales},

author = {Marcus Lechner and Astrid I. Nickel and Stefanie Wehner and Konstantin Riege and Nicolas Wieseke and Benedikt M. Beckmann and Roland K. Hartmann and Manja Marz},

doi = {10.1186/1471-2164-15-522},

year  = {2014},

date = {2014-06-25},

urldate = {2014-06-25},

journal = {BMC Genomics},

volume = {15},

pages = {522},

abstract = {The Aquificales are a diverse group of thermophilic bacteria that thrive in terrestrial and marine hydrothermal environments. They can be divided into the families Aquificaceae, Desulfurobacteriaceae and Hydrogenothermaceae. Although eleven fully sequenced and assembled genomes are available, only little is known about this taxonomic order in terms of RNA metabolism. In this work, we compare the available genomes, extend their protein annotation, identify regulatory sequences, annotate non-coding RNAs (ncRNAs) of known function, predict novel ncRNA candidates, show idiosyncrasies of the genetic decoding machinery, present two different types of transfer-messenger RNAs and variations of the CRISPR systems. Furthermore, we performed a phylogenetic analysis of the Aquificales based on entire genome sequences, and extended this by a classification among all bacteria using 16S rRNA sequences and a set of orthologous proteins.Combining several in silico features (e.g. conserved and stable secondary structures, GC-content, comparison based on multiple genome alignments) with an in vivo dRNA-seq transcriptome analysis of Aquifex aeolicus, we predict roughly 100 novel ncRNA candidates in this bacterium. We have here re-analyzed the Aquificales, a group of bacteria thriving in extreme environments, sharing the feature of a small, compact genome with a reduced number of protein and ncRNA genes. We present several classical ncRNAs and riboswitch candidates. By combining in silico analysis with dRNA-seq data of A. aeolicus we predict nearly 100 novel ncRNA candidates.},

keywords = {alignment, annotation, assembly, bacteria, classification, ncRNAs, phylogenetics},

pubstate = {published},

tppubtype = {article}

}

@article{Wehner:14b,

title = {pRNA: NoRC-associated RNA of rRNA operons},

author = {Stefanie Wehner and Anja K Dörrich and Philipp Ciba and Annegret Wilde and Manja Marz},

doi = {10.4161/rna.27448},

year  = {2013},

date = {2013-12-20},

urldate = {2013-12-20},

journal = {RNA Biol},

volume = {11},

pages = {3--9},

abstract = {Promoter-associated RNAs (pRNAs) are a family of ~90-100 nt-long divergent RNAs overlapping the promoter of the rRNA (rDNA) operon. pRNA transcripts interact with TIP5, a component of the chromatin remodeling complex NoRC, which recruits enzymes for heterochromatin formation and mediates silencing of rRNA genes. Here we present a comprehensive analysis of pRNA homologs, including different versions per species, as result of in silico studies in available metazoan genome assemblies. Comparative sequence analysis and secondary structure prediction ended up in two possible secondary structures, which let us assume a possible dual function of pRNAs for regulation of rRNA operons. Furthermore, we validated parts of our computational predictions experimentally by RT-PCR and sequencing. A representative seed alignment of the pRNA family, annotated with possible secondary structures was released to the Rfam database.},

keywords = {alignment, assembly, ncRNAs, RNA / transcriptomics, RNA structure},

pubstate = {published},

tppubtype = {article}

}

@article{Vierna:13,

title = {Systematic analysis and evolution of 5S ribosomal DNA in metazoans},

author = {Joaquin Vierna and Stefanie Wehner and Christian {Höner zu Siederdissen} and Andrés Martínez-Lage and Manja Marz},

doi = {10.1038/hdy.2013.63},

year  = {2013},

date = {2013-07-10},

urldate = {2013-07-10},

journal = {Heredity},

volume = {111},

pages = {410--421},

abstract = {Several studies on 5S ribosomal DNA (5S rDNA) have been focused on a subset of the following features in mostly one organism: number of copies, pseudogenes, secondary structure, promoter and terminator characteristics, genomic arrangements, types of non-transcribed spacers and evolution. In this work, we systematically analyzed 5S rDNA sequence diversity in available metazoan genomes, and showed organism-specific and evolutionary-conserved features. Putatively functional sequences (12,766) from 97 organisms allowed us to identify general features of this multigene family in animals. Interestingly, we show that each mammal species has a highly conserved (housekeeping) 5S rRNA type and many variable ones. The genomic organization of 5S rDNA is still under debate. Here, we report the occurrence of several paralog 5S rRNA sequences in 58 of the examined species, and a flexible genome organization of 5S rDNA in animals. We found heterogeneous 5S rDNA clusters in several species, supporting the hypothesis of an exchange of 5S rDNA from one locus to another. A rather high degree of variation of upstream, internal and downstream putative regulatory regions appears to characterize metazoan 5S rDNA. We systematically studied the internal promoters and described three different types of termination signals, as well as variable distances between the coding region and the typical termination signal. Finally, we present a statistical method for detection of linkage among noncoding RNA (ncRNA) gene families. This method showed no evolutionary-conserved linkage among 5S rDNAs and any other ncRNA genes within Metazoa, even though we found 5S rDNA to be linked to various ncRNAs in several clades.},

keywords = {DNA / genomics, evolution, ncRNAs, RNA structure},

pubstate = {published},

tppubtype = {article}

}

@article{Gimpel:12,

title = {SR1 - a small RNA with two remarkably conserved functions},

author = {Matthias Gimpel and Heike Preis and Emanuel Barth and Lydia Gramzow and Sabine Brantl},

doi = {10.1093/nar/gks895},

year  = {2012},

date = {2012-10-02},

urldate = {2012-01-01},

journal = {Nucleic Acids Res},

volume = {40},

pages = {11659--11672},

abstract = {SR1 is a dual-function sRNA that acts as a base-pairing regulatory RNA on the ahrC mRNA and as a peptide-encoding mRNA on the gapA operon. The SR1-encoded peptide SR1P binds GapA thereby stabilizing gapA mRNA. Under glycolytic conditions, SR1 transcription is repressed by CcpN and CcpA. A computer-based search identified 23 SR1 homologues in Bacillus, Geobacillus, Anoxybacillus and Brevibacillus species. All homologues share a high structural identity with Bacillus subtilis SR1, and the encoded SR1P peptides are highly similar. In the Bacillus cereus group, the sr1p region is present in triplicate or duplicate resulting in longer SR1 species. In all cases, sr1 expression is under control of CcpN, and transcriptional lacZ fusions of nine examined SR1 homologues were sensitive to glucose. Two homologues showed an additional glucose-independent repression by CcpN and an unknown factor. A total of 10 out of 11 tested SR1P homologues complemented a B. subtilis Δsr1 strain in their ability to stabilize gapA mRNA, but only five of them bound GapA tightly. In vitro binding assays with six SR1/ahrC pairs suggest that-despite divergent primary sequences-the base-pairing function is also preserved. In summary, SR1 is an sRNA with two functions that have been conserved over ≈1 billion years.},

keywords = {bacteria, ncRNAs},

pubstate = {published},

tppubtype = {article}

}

@article{Beckmann:12,

title = {A pRNA-induced structural rearrangement triggers 6S-1 RNA release from RNA polymerase in \textit{Bacillus subtilis}},

author = {Benedikt M. Beckmann and Philipp G. Hoch and Manja Marz and Dagmar K. Willkomm and Margarita Salas and Roland K. Hartmann},

doi = {10.1038/emboj.2012.23},

year  = {2012},

date = {2012-01-01},

urldate = {2012-01-01},

journal = {EMBO J},

volume = {31},

pages = {1727--1738},

abstract = {Bacillus subtilis 6S-1 RNA binds to the housekeeping RNA polymerase (σ(A)-RNAP) and directs transcription of short 'product' RNAs (pRNAs). Here, we demonstrate that once newly synthesized pRNAs form a sufficiently stable duplex with 6S-1 RNA, a structural rearrangement is induced in cis, which involves base-pairing between sequences in the 5'-portion of the central bulge and nucleotides that become available as a result of pRNA invasion. The rearrangement decreases 6S-1 RNA affinity for σ(A)-RNAP. Among the pRNA length variants synthesized by σ(A)-RNAP (up to ∼14 nt), only the longer ones, such as 12-14-mers, form a duplex with 6S-1 RNA that is sufficiently long-lived to induce the rearrangement. Yet, an LNA (locked nucleic acid) 8-mer can induce the same rearrangement due to conferring increased duplex stability. We propose that an interplay of rate constants for polymerization (k(pol)), for pRNA:6S-1 RNA hybrid duplex dissociation (k(off)) and for the rearrangement (k(conf)) determines whether pRNAs dissociate or rearrange 6S-1 structure to trigger 6S-1 RNA release from σ(A)-RNAP. A bioinformatic screen suggests that essentially all bacterial 6S RNAs have the potential to undergo a pRNA-induced structural rearrangement.},

keywords = {bacteria, ncRNAs},

pubstate = {published},

tppubtype = {article}

}

@article{Marz:11,

title = {Animal snoRNAs and scaRNAs with exceptional structures},

author = {Manja Marz and Andreas R. Gruber and Christian {Höner zu Siederdissen} and Fabian Amman and Stefan Badelt and Sebastian Bartschat and Stephan H. Bernhart and Wolfgang Beyer and Stephanie Kehr and Ronny Lorenz and Andrea Tanzer and Dilmurat Yusuf and Hakim Tafer and Ivo L. Hofacker and Peter F. Stadler},

doi = {10.4161/rna.8.6.16603},

year  = {2011},

date = {2011-11-01},

urldate = {2011-11-01},

journal = {RNA Biol},

volume = {8},

pages = {938--946},

abstract = {The overwhelming majority of small nucleolar RNAs (snoRNAs) fall into two clearly defined classes characterized by distinctive secondary structures and sequence motifs. A small group of diverse ncRNAs, however, shares the hallmarks of one or both classes of snoRNAs but differs substantially from the norm in some respects. Here, we compile the available information on these exceptional cases, conduct a thorough homology search throughout the available metazoan genomes, provide improved and expanded alignments, and investigate the evolutionary histories of these ncRNA families as well as their mutual relationships.},

keywords = {alignment, ncRNAs, RNA / transcriptomics, RNA structure},

pubstate = {published},

tppubtype = {article}

}

@article{Bateman:11,

title = {RNAcentral: A vision for an international database of RNA sequences},

author = {Alex Bateman and Shipra Agrawal and Ewan Birney and Elspeth A. Bruford and Janusz M. Bujnicki and Guy Cochrane and James R. Cole and Marcel E. Dinger and Anton J. Enright and Paul P. Gardner and Daniel Gautheret and Sam Griffiths-Jones and Jen Harrow and Javier Herrero and Ian H. Holmes and Hsien-Da Huang and Krystyna A. Kelly and Paul Kersey and Ana Kozomara and Todd M. Lowe and Manja Marz and Simon Moxon and Kim D. Pruitt and Tore Samuelsson and Peter F. Stadler and Albert J. Vilella and Jan-Hinnerk Vogel and Kelly P. Williams and Mathew W. Wright and Christian Zwieb},

doi = {10.1261/rna.2750811},

year  = {2011},

date = {2011-09-22},

urldate = {2011-09-22},

journal = {RNA},

volume = {17},

pages = {1941--1946},

abstract = {During the last decade there has been a great increase in the number of noncoding RNA genes identified, including new classes such as microRNAs and piRNAs. There is also a large growth in the amount of experimental characterization of these RNA components. Despite this growth in information, it is still difficult for researchers to access RNA data, because key data resources for noncoding RNAs have not yet been created. The most pressing omission is the lack of a comprehensive RNA sequence database, much like UniProt, which provides a comprehensive set of protein knowledge. In this article we propose the creation of a new open public resource that we term RNAcentral, which will contain a comprehensive collection of RNA sequences and fill an important gap in the provision of biomedical databases. We envision RNA researchers from all over the world joining a federated RNAcentral network, contributing specialized knowledge and databases. RNAcentral would centralize key data that are currently held across a variety of databases, allowing researchers instant access to a single, unified resource. This resource would facilitate the next generation of RNA research and help drive further discoveries, including those that improve food production and human and animal health. We encourage additional RNA database resources and research groups to join this effort. We aim to obtain international network funding to further this endeavor.},

keywords = {database, ncRNAs, RNA / transcriptomics},

pubstate = {published},

tppubtype = {article}

}

@article{Dalloul:10,

title = {Multi-platform next-generation sequencing of the domestic turkey (\textit{Meleagris gallopavo}): genome assembly and analysis},

author = {Rami A. Dalloul and Julie A. Long and Aleksey V. Zimin and Luqman Aslam and Kathryn Beal and Le Ann Blomberg and Pascal Bouffard and David W. Burt and Oswald Crasta and Richard P. M. A. Crooijmans and Kristal Cooper and Roger A. Coulombe and Supriyo De and Mary E. Delany and Jerry B. Dodgson and Jennifer J. Dong and Clive Evans and Karin M. Frederickson and Paul Flicek and Liliana Florea and Otto Folkerts and Martien A. M. Groenen and Tim T. Harkins and Javier Herrero and Steve Hoffmann and Hendrik-Jan Megens and Andrew Jiang and Pieter Jong and Pete Kaiser and Heebal Kim and Kyu-Won Kim and Sungwon Kim and David Langenberger and Mi-Kyung Lee and Taeheon Lee and Shrinivasrao Mane and Guillaume Marcais and Manja Marz and Audrey P. McElroy and Thero Modise and Mikhail Nefedov and Cédric Notredame and Ian R. Paton and William S. Payne and Geo Pertea and Dennis Prickett and Daniela Puiu and Dan Qioa and Emanuele Raineri and Magali Ruffier and Steven L. Salzberg and Michael C. Schatz and Chantel Scheuring and Carl J. Schmidt and Steven Schroeder and Stephen M. J. Searle and Edward J. Smith and Jacqueline Smith and Tad S. Sonstegard and Peter F. Stadler and Hakim Tafer and Zhijian Jake Tu and Curtis P. Van Tassell and Albert J. Vilella and Kelly P. Williams and James A. Yorke and Liqing Zhang and Hong-Bin Zhang and Xiaojun Zhang and Yang Zhang and Kent M. Reed},

doi = {10.1371/journal.pbio.1000475},

year  = {2010},

date = {2010-09-07},

urldate = {2010-09-07},

journal = {PLoS Biol},

volume = {8},

abstract = {A synergistic combination of two next-generation sequencing platforms with a detailed comparative BAC physical contig map provided a cost-effective assembly of the genome sequence of the domestic turkey (Meleagris gallopavo). Heterozygosity of the sequenced source genome allowed discovery of more than 600,000 high quality single nucleotide variants. Despite this heterozygosity, the current genome assembly (∼1.1 Gb) includes 917 Mb of sequence assigned to specific turkey chromosomes. Annotation identified nearly 16,000 genes, with 15,093 recognized as protein coding and 611 as non-coding RNA genes. Comparative analysis of the turkey, chicken, and zebra finch genomes, and comparing avian to mammalian species, supports the characteristic stability of avian genomes and identifies genes unique to the avian lineage. Clear differences are seen in number and variety of genes of the avian immune system where expansions and novel genes are less frequent than examples of gene loss. The turkey genome sequence provides resources to further understand the evolution of vertebrate genomes and genetic variation underlying economically important quantitative traits in poultry. This integrated approach may be a model for providing both gene and chromosome level assemblies of other species with agricultural, ecological, and evolutionary interest.},

keywords = {alignment, annotation, assembly, DNA / genomics, ncRNAs},

pubstate = {published},

tppubtype = {article}

}

@article{Yusuf:10,

title = {Bcheck: a wrapper tool for detecting RNase P RNA genes},

author = {Dilmurat Yusuf and Manja Marz and Peter F Stadler and Ivo L Hofacker},

url = {http://rna.tbi.univie.ac.at/bcheck},

doi = {10.1186/1471-2164-11-432},

year  = {2010},

date = {2010-07-13},

urldate = {2010-07-13},

journal = {BMC Genomics},

volume = {11},

pages = {432},

abstract = {Effective bioinformatics solutions are needed to tackle challenges posed by industrial-scale genome annotation. We present Bcheck, a wrapper tool which predicts RNase P RNA genes by combining the speed of pattern matching and sensitivity of covariance models. The core of Bcheck is a library of subfamily specific descriptor models and covariance models. Scanning all microbial genomes in GenBank identifies RNase P RNA genes in 98% of 1024 microbial chromosomal sequences within just 4 hours on single CPU. Comparing to existing annotations found in 387 of the GenBank files, Bcheck predictions have more intact structure and are automatically classified by subfamily membership. For eukaryotic chromosomes Bcheck could identify the known RNase P RNA genes in 84 out of 85 metazoan genomes and 19 out of 21 fungi genomes. Bcheck predicted 37 novel eukaryotic RNase P RNA genes, 32 of which are from fungi. Gene duplication events are observed in at least 20 metazoan organisms. Scanning of meta-genomic data from the Global Ocean Sampling Expedition, comprising over 10 million sample sequences (18 Gigabases), predicted 2909 unique genes, 98% of which fall into ancestral bacteria A type of RNase P RNA and 66% of which have no close homolog to known prokaryotic RNase P RNA. The combination of efficient filtering by means of a descriptor-based search and subsequent construction of a high-quality gene model by means of a covariance model provides an efficient method for the detection of RNase P RNA genes in large-scale sequencing data. Bcheck is implemented as webserver and can also be downloaded for local use from http://rna.tbi.univie.ac.at/bcheck.},

keywords = {annotation, bacteria, classification, fungi, ncRNAs, RNA / transcriptomics, software},

pubstate = {published},

tppubtype = {article}

}

@article{Marz:09a,

title = {Comparative analysis of eukaryotic U3 snoRNA},

author = {Manja Marz and Peter F Stadler},

doi = {10.4161/rna.6.5.9607},

year  = {2009},

date = {2009-11-01},

urldate = {2009-11-01},

journal = {RNA Biol},

volume = {6},

pages = {503--507},

abstract = {The U3 snoRNA is an exceptional box C/D snoRNA, which is involved in pre-rRNA processing without directing chemical modifications. We report here on a comprehensive computational survey resulting in U3 sequences for more than 90 additional eukaryotes. This extended data basis is used to improve the secondary structure models. The detailed investigation of the structural variation of U3 snoRNAs turns out to be much more extensive than previously thought. Many fungal U3 genes, in addition, contain introns. U3 promoters are snRNA-like but show substantial variations even between related species.},

keywords = {ncRNAs, RNA structure},

pubstate = {published},

tppubtype = {article}

}

@article{Copeland:09,

title = {Homology-based annotation of non-coding RNAs in the genomes of \textit{Schistosoma mansoni} and \textit{Schistosoma japonicum}},

author = {Claudia S. Copeland and Manja Marz and Dominic Rose and Jana Hertel and Paul J. Brindley and Clara Bermudez Santana and Stephanie Kehr and Camille Stephan-Otto Attolini and Peter F. Stadler},

doi = {10.1186/1471-2164-10-464},

year  = {2009},

date = {2009-10-08},

urldate = {2009-10-08},

journal = {BMC Genomics},

volume = {10},

pages = {464},

abstract = {Schistosomes are trematode parasites of the phylum Platyhelminthes. They are considered the most important of the human helminth parasites in terms of morbidity and mortality. Draft genome sequences are now available for Schistosoma mansoni and Schistosoma japonicum. Non-coding RNA (ncRNA) plays a crucial role in gene expression regulation, cellular function and defense, homeostasis, and pathogenesis. The genome-wide annotation of ncRNAs is a non-trivial task unless well-annotated genomes of closely related species are already available. A homology search for structured ncRNA in the genome of S. mansoni resulted in 23 types of ncRNAs with conserved primary and secondary structure. Among these, we identified rRNA, snRNA, SL RNA, SRP, tRNAs and RNase P, and also possibly MRP and 7SK RNAs. In addition, we confirmed five miRNAs that have recently been reported in S. japonicum and found two additional homologs of known miRNAs. The tRNA complement of S. mansoni is comparable to that of the free-living planarian Schmidtea mediterranea, although for some amino acids differences of more than a factor of two are observed: Leu, Ser, and His are overrepresented, while Cys, Meth, and Ile are underrepresented in S. mansoni. On the other hand, the number of tRNAs in the genome of S. japonicum is reduced by more than a factor of four. Both schistosomes have a complete set of minor spliceosomal snRNAs. Several ncRNAs that are expected to exist in the S. mansoni genome were not found, among them the telomerase RNA, vault RNAs, and Y RNAs. The ncRNA sequences and structures presented here represent the most complete dataset of ncRNA from any lophotrochozoan reported so far. This data set provides an important reference for further analysis of the genomes of schistosomes and indeed eukaryotic genomes at large.},

keywords = {annotation, ncRNAs, RNA structure},

pubstate = {published},

tppubtype = {article}

}

@article{Marz:09,

title = {Evolution of 7SK RNA and its protein partners in metazoa},

author = {Manja Marz and Alexander Donath and Nina Verstraete and Van Trung Nguyen and Peter F Stadler and Olivier Bensaude},

doi = {10.1093/molbev/msp198},

year  = {2009},

date = {2009-09-04},

urldate = {2009-09-04},

journal = {Mol Biol Evol},

volume = {26},

number = {12},

pages = {2821--2830},

abstract = {7SK RNA is a key player in the regulation of polymerase II transcription. 7SK RNA was considered as a highly conserved vertebrate innovation. The discovery of poorly conserved homologs in several insects and lophotrochozoans, however, implies a much earlier evolutionary origin. The mechanism of 7SK function requires interaction with the proteins HEXIM and La-related protein 7. Here, we present a comprehensive computational analysis of these two proteins in metazoa, and we extend the collection of 7SK RNAs by several additional candidates. In particular, we describe 7SK homologs in Caenorhabditis species. Furthermore, we derive an improved secondary structure model of 7SK RNA, which shows that the structure is quite well-conserved across animal phyla despite the extreme divergence at sequence level.},

keywords = {evolution, ncRNAs, proteins, RNA structure},

pubstate = {published},

tppubtype = {article}

}

@article{Hiller:09,

title = {Conserved introns reveal novel transcripts in \textit{Drosophila melanogaster}},

author = {Michael Hiller and Sven Findeiss and Sandro Lein and Manja Marz and Claudia Nickel and Dominic Rose and Christine Schulz and Rolf Backofen and Sonja J Prohaska and Gunter Reuter and Peter F Stadler},

doi = {10.1101/gr.090050.108},

year  = {2009},

date = {2009-05-20},

urldate = {2009-05-20},

journal = {Genome Res},

volume = {19},

pages = {1289--1300},

abstract = {Noncoding RNAs that are-like mRNAs-spliced, capped, and polyadenylated have important functions in cellular processes. The inventory of these mRNA-like noncoding RNAs (mlncRNAs), however, is incomplete even in well-studied organisms, and so far, no computational methods exist to predict such RNAs from genomic sequences only. The subclass of these transcripts that is evolutionarily conserved usually has conserved intron positions. We demonstrate here that a genome-wide comparative genomics approach searching for short conserved introns is capable of identifying conserved transcripts with a high specificity. Our approach requires neither an open reading frame nor substantial sequence or secondary structure conservation in the surrounding exons. Thus it identifies spliced transcripts in an unbiased way. After applying our approach to insect genomes, we predict 369 introns outside annotated coding transcripts, of which 131 are confirmed by expressed sequence tags (ESTs) and/or noncoding FlyBase transcripts. Of the remaining 238 novel introns, about half are associated with protein-coding genes-either extending coding or untranslated regions or likely belonging to unannotated coding genes. The remaining 129 introns belong to novel mlncRNAs that are largely unstructured. Using RT-PCR, we verified seven of 12 tested introns in novel mlncRNAs and 11 of 17 introns in novel coding genes. The expression level of all verified mlncRNA transcripts is low but varies during development, which suggests regulation. As conserved introns indicate both purifying selection on the exon-intron structure and conserved expression of the transcript in related species, the novel mlncRNAs are good candidates for functional transcripts.},

keywords = {insects, ncRNAs, RNA structure},

pubstate = {published},

tppubtype = {article}

}

@article{Hertel:09,

title = {Non-coding RNA annotation of the genome of \textit{Ŧrichoplax adhaerens}},

author = {Jana Hertel and Danielle Jong and Manja Marz and Dominic Rose and Hakim Tafer and Andrea Tanzer and Bernd Schierwater and Peter F Stadler},

doi = {10.1093/nar/gkn1084},

year  = {2009},

date = {2009-01-26},

urldate = {2009-01-01},

journal = {Nucleic Acids Res},

volume = {37},

number = {5},

pages = {1602--1615},

abstract = {A detailed annotation of non-protein coding RNAs is typically missing in initial releases of newly sequenced genomes. Here we report on a comprehensive ncRNA annotation of the genome of Trichoplax adhaerens, the presumably most basal metazoan whose genome has been published to-date. Since blast identified only a small fraction of the best-conserved ncRNAs--in particular rRNAs, tRNAs and some snRNAs--we developed a semi-global dynamic programming tool, GotohScan, to increase the sensitivity of the homology search. It successfully identified the full complement of major and minor spliceosomal snRNAs, the genes for RNase P and MRP RNAs, the SRP RNA, as well as several small nucleolar RNAs. We did not find any microRNA candidates homologous to known eumetazoan sequences. Interestingly, most ncRNAs, including the pol-III transcripts, appear as single-copy genes or with very small copy numbers in the Trichoplax genome.},

keywords = {annotation, ncRNAs},

pubstate = {published},

tppubtype = {article}

}

@article{Jones:09,

title = {A survey of nematode SmY RNAs},

author = {Thomas A Jones and Wolfgang Otto and Manja Marz and Sean R Eddy and Peter F Stadler},

doi = {10.4161/rna.6.1.7634},

year  = {2009},

date = {2009-01-01},

urldate = {2009-01-01},

journal = {RNA Biol},

volume = {6},

pages = {5--8},

abstract = {SmY RNAs are a family of approximately 70-90 nt small nuclear RNAs found in nematodes. In C. elegans, SmY RNAs copurify in a small ribonucleoprotein (snRNP) complex related to the SL1 and SL2 snRNPs that are involved in nematode mRNA trans-splicing. Here we describe a comprehensive computational analysis of SmY RNA homologs found in the currently available genome sequences. We identify homologs in all sequenced nematode genomes in class Chromadorea. We are unable to identify homologs in a more distantly related nematode species, Trichinella spiralis (class: Dorylaimia), and in representatives of non-nematode phyla that use trans-splicing. Using comparative RNA sequence analysis, we infer a conserved consensus SmY RNA secondary structure consisting of two stems flanking a consensus Sm protein binding site. A representative seed alignment of the SmY RNA family, annotated with the inferred consensus secondary structure, has been deposited with the Rfam RNA families database.},

keywords = {alignment, ncRNAs, RNA / transcriptomics, RNA structure, splicing},

pubstate = {published},

tppubtype = {article}

}

@article{Marz:08,

title = {Evolution of spliceosomal snRNA genes in metazoan animals},

author = {Manja Marz and Toralf Kirsten and Peter F Stadler},

doi = {10.1007/s00239-008-9149-6},

year  = {2008},

date = {2008-11-22},

urldate = {2008-11-22},

journal = {J Mol Evol},

volume = {67},

pages = {594--607},

abstract = {While studies of the evolutionary histories of protein families are commonplace, little is known on noncoding RNAs beyond microRNAs and some snoRNAs. Here we investigate in detail the evolutionary history of the nine spliceosomal snRNA families (U1, U2, U4, U5, U6, U11, U12, U4atac, and U6atac) across the completely or partially sequenced genomes of metazoan animals. Representatives of the five major spliceosomal snRNAs were found in all genomes. None of the minor splicesomal snRNAs were detected in nematodes or in the shotgun traces of Oikopleura dioica, while in all other animal genomes at most one of them is missing. Although snRNAs are present in multiple copies in most genomes, distinguishable paralogue groups are not stable over long evolutionary times, although they appear independently in several clades. In general, animal snRNA secondary structures are highly conserved, albeit, in particular, U11 and U12 in insects exhibit dramatic variations. An analysis of genomic context of snRNAs reveals that they behave like mobile elements, exhibiting very little syntenic conservation.},

keywords = {evolution, insects, ncRNAs, RNA structure, splicing},

pubstate = {published},

tppubtype = {article}

}

@article{Marz:07,

title = {U7 snRNAs: a computational survey},

author = {Manja Marz and Axel Mosig and Bärbel M R Stadler and Peter F Stadler},

doi = {10.1016/S1672-0229(08)60006-6},

year  = {2008},

date = {2008-02-08},

urldate = {2008-02-08},

journal = {Genomics Proteomics Bioinformatics},

volume = {5},

number = {3-4},

pages = {187--195},

abstract = {U7 small nuclear RNA (snRNA) sequences have been described only for a handful of animal species in the past. Here we describe a computational search for functional U7 snRNA genes throughout vertebrates including the upstream sequence elements characteristic for snRNAs transcribed by polymerase II. Based on the results of this search, we discuss the high variability of U7 snRNAs in both sequence and structure, and report on an attempt to find U7 snRNA sequences in basal deuterostomes and non-drosophilids insect genomes based on a combination of sequence, structure, and promoter features. Due to the extremely short sequence and the high variability in both sequence and structure, no unambiguous candidates were found. These results cast doubt on putative U7 homologs in even more distant organisms that are reported in the most recent release of the Rfam database.},

keywords = {evolution, insects, ncRNAs, RNA structure},

pubstate = {published},

tppubtype = {article}

}

@article{Gruber:08,

title = {Invertebrate 7SK snRNAs},

author = {Andreas R Gruber and Dorota Koper-Emde and Manja Marz and Hakim Tafer and Stephan Bernhart and Gregor Obernosterer and Axel Mosig and Ivo L Hofacker and Peter F Stadler and Bernd-Joachim Benecke},

doi = {10.1007/s00239-007-9052-6},

year  = {2008},

date = {2008-01-12},

urldate = {2008-01-12},

journal = {J Mol Evol},

volume = {66},

pages = {107--115},

abstract = {7SK RNA is a highly abundant noncoding RNA in mammalian cells whose function in transcriptional regulation has only recently been elucidated. Despite its highly conserved sequence throughout vertebrates, all attempts to discover 7SK RNA homologues in invertebrate species have failed so far. Here we report on a combined experimental and computational survey that succeeded in discovering 7SK RNAs in most of the major deuterostome clades and in two protostome phyla: mollusks and annelids. Despite major efforts, no candidates were found in any of the many available ecdysozoan genomes, however. The additional sequence data confirm the evolutionary conservation and hence functional importance of the previously described 3' and 5' stem-loop motifs, and provide evidence for a third, structurally well-conserved domain.},

keywords = {evolution, ncRNAs},

pubstate = {published},

tppubtype = {article}

}

@article{Washietl:07,

title = {Structured RNAs in the ENCODE selected regions of the human genome},

author = {Stefan Washietl and Jakob S Pedersen and Jan O Korbel and Claudia Stocsits and Andreas R Gruber and Jörg Hackermüller and Jana Hertel and Manja Lindemeyer and Kristin Reiche and Andrea Tanzer and Catherine Ucla and Carine Wyss and Stylianos E Antonarakis and France Denoeud and Julien Lagarde and Jorg Drenkow and Philipp Kapranov and Thomas R Gingeras and Roderic Guigó and Michael Snyder and Mark B Gerstein and Alexandre Reymond and Ivo L Hofacker and Peter F Stadler},

url = {https://www.tbi.univie.ac.at/papers/SUPPLEMENTS/ENCODE/},

doi = {10.1101/gr.5650707},

year  = {2007},

date = {2007-01-01},

urldate = {2007-01-01},

journal = {Genome Res},

volume = {17},

pages = {852--864},

abstract = {Functional RNA structures play an important role both in the context of noncoding RNA transcripts as well as regulatory elements in mRNAs. Here we present a computational study to detect functional RNA structures within the ENCODE regions of the human genome. Since structural RNAs in general lack characteristic signals in primary sequence, comparative approaches evaluating evolutionary conservation of structures are most promising. We have used three recently introduced programs based on either phylogenetic-stochastic context-free grammar (EvoFold) or energy directed folding (RNAz and AlifoldZ), yielding several thousand candidate structures (corresponding to approximately 2.7% of the ENCODE regions). EvoFold has its highest sensitivity in highly conserved and relatively AU-rich regions, while RNAz favors slightly GC-rich regions, resulting in a relatively small overlap between methods. Comparison with the GENCODE annotation points to functional RNAs in all genomic contexts, with a slightly increased density in 3'-UTRs. While we estimate a significant false discovery rate of approximately 50%-70% many of the predictions can be further substantiated by additional criteria: 248 loci are predicted by both RNAz and EvoFold, and an additional 239 RNAz or EvoFold predictions are supported by the (more stringent) AlifoldZ algorithm. Five hundred seventy RNAz structure predictions fall into regions that show signs of selection pressure also on the sequence level (i.e., conserved elements). More than 700 predictions overlap with noncoding transcripts detected by oligonucleotide tiling arrays. One hundred seventy-five selected candidates were tested by RT-PCR in six tissues, and expression could be verified in 43 cases (24.6%).},

keywords = {annotation, evolution, ncRNAs, RNA structure},

pubstate = {published},

tppubtype = {article}

}

@article{Hertel:06,

title = {The expansion of the metazoan microRNA repertoire},

author = {Jana Hertel and Manja Lindemeyer and Kristin Missal and Claudia Fried and Andrea Tanzer and Christoph Flamm and Ivo L. Hofacker and Peter F. Stadler and Students Bioinformatics Computer Labs 2004 & 2005},

doi = {10.1186/1471-2164-7-25},

year  = {2006},

date = {2006-02-15},

urldate = {2006-02-15},

journal = {BMC Genomics},

volume = {7},

pages = {25},

abstract = {MicroRNAs have been identified as crucial regulators in both animals and plants. Here we report on a comprehensive comparative study of all known miRNA families in animals. We expand the MicroRNA Registry 6.0 by more than 1000 new homologs of miRNA precursors whose expression has been verified in at least one species. Using this uniform data basis we analyze their evolutionary history in terms of individual gene phylogenies and in terms of preservation of genomic nearness across species. This allows us to reliably identify microRNA clusters that are derived from a common transcript. We identify three episodes of microRNA innovation that correspond to major developmental innovations: A class of about 20 miRNAs is common to protostomes and deuterostomes and might be related to the advent of bilaterians. A second large wave of innovations maps to the branch leading to the vertebrates. The third significant outburst of miRNA innovation coincides with placental (eutherian) mammals. In addition, we observe the expected expansion of the microRNA inventory due to genome duplications in early vertebrates and in an ancestral teleost. The non-local duplications in the vertebrate ancestor are predated by local (tandem) duplications leading to the formation of about a dozen ancient microRNA clusters. Our results suggest that microRNA innovation is an ongoing process. Major expansions of the metazoan miRNA repertoire coincide with the advent of bilaterians, vertebrates, and (placental) mammals.},

keywords = {ncRNAs, phylogenetics},

pubstate = {published},

tppubtype = {article}

}