2025
Triebel, Sandra; Eulenfeld, Tom; Ontiveros-Palacios, Nancy; Sweeney, Blake; Tautz, Norbert; Marz, Manja
First full-genome alignment representative for the genus Pestivirus Journal Article
In: bioRxiv, 2025.
Abstract | Links | BibTeX | Tags: alignment, evolution, phylogenetics, RNA structure, RNA-RNA interactions, viruses
@article{nokey_77,
title = {First full-genome alignment representative for the genus \textit{Pestivirus}},
author = {Sandra Triebel and Tom Eulenfeld and Nancy Ontiveros-Palacios and Blake Sweeney and Norbert Tautz and Manja Marz},
url = {https://doi.org/10.5281/zenodo.15490752},
doi = {10.1101/2025.05.22.655560},
year = {2025},
date = {2025-05-27},
journal = {bioRxiv},
abstract = {The members of the genus Pestivirus in the family Flaviviridae comprise economically important pathogens of life stock like classical swine fever (CSFV) and bovine viral diarrhea virus (BVDV). Intense research over the last years revealed that at least 11 recognized and eight proposed pestivirus species exist. The single-stranded, positive-sense RNA genome encodes for one large polyprotein which is processed by viral and cell-derived proteases into 12 mature proteins. Besides its protein-coding function, the RNA genome also contains RNA secondary structures with critical importance for various stages of the viral life cycle. Some of those RNA secondary structures, like the internal ribosome entry site (IRES) and a 3’ stem-loop essential for genome replication, had already been studied for a few individual pestiviruses.
In this study, we provide the first genome-wide multiple sequence alignment (MSA) including all known pestivirus species (accepted and tentative). Moreover, we performed a comprehensive analysis of RNA secondary structures phylogenetically conserved across the complete genus. While showing well-described structures, like a 5’ stem-loop structure, the IRES element, and the 3’ stem loop SL I to be conserved between all pestiviruses, other RNA secondary structures in the 3’ untranslated region (UTR) were only conserved in subsets of the species. We identified 29 novel phylogenetically conserved RNA secondary structures in the protein-coding region, with so far unresolved functional importance. The microRNA binding site for miR-17 was previously known in species A, B, and C; in this study, we identified it in ten additional species, but not in species K, S, Q, and R. Another interesting finding is the identification of a putative long-distance RNA interaction between the IRES and the 3’ end of the genome. These results together with the now available comprehensive multiple sequence alignment including all 19 pestivirus species, represent a valuable resource for future research and diagnostic purposes.},
keywords = {alignment, evolution, phylogenetics, RNA structure, RNA-RNA interactions, viruses},
pubstate = {published},
tppubtype = {article}
}
The members of the genus Pestivirus in the family Flaviviridae comprise economically important pathogens of life stock like classical swine fever (CSFV) and bovine viral diarrhea virus (BVDV). Intense research over the last years revealed that at least 11 recognized and eight proposed pestivirus species exist. The single-stranded, positive-sense RNA genome encodes for one large polyprotein which is processed by viral and cell-derived proteases into 12 mature proteins. Besides its protein-coding function, the RNA genome also contains RNA secondary structures with critical importance for various stages of the viral life cycle. Some of those RNA secondary structures, like the internal ribosome entry site (IRES) and a 3’ stem-loop essential for genome replication, had already been studied for a few individual pestiviruses.
In this study, we provide the first genome-wide multiple sequence alignment (MSA) including all known pestivirus species (accepted and tentative). Moreover, we performed a comprehensive analysis of RNA secondary structures phylogenetically conserved across the complete genus. While showing well-described structures, like a 5’ stem-loop structure, the IRES element, and the 3’ stem loop SL I to be conserved between all pestiviruses, other RNA secondary structures in the 3’ untranslated region (UTR) were only conserved in subsets of the species. We identified 29 novel phylogenetically conserved RNA secondary structures in the protein-coding region, with so far unresolved functional importance. The microRNA binding site for miR-17 was previously known in species A, B, and C; in this study, we identified it in ten additional species, but not in species K, S, Q, and R. Another interesting finding is the identification of a putative long-distance RNA interaction between the IRES and the 3’ end of the genome. These results together with the now available comprehensive multiple sequence alignment including all 19 pestivirus species, represent a valuable resource for future research and diagnostic purposes.
In this study, we provide the first genome-wide multiple sequence alignment (MSA) including all known pestivirus species (accepted and tentative). Moreover, we performed a comprehensive analysis of RNA secondary structures phylogenetically conserved across the complete genus. While showing well-described structures, like a 5’ stem-loop structure, the IRES element, and the 3’ stem loop SL I to be conserved between all pestiviruses, other RNA secondary structures in the 3’ untranslated region (UTR) were only conserved in subsets of the species. We identified 29 novel phylogenetically conserved RNA secondary structures in the protein-coding region, with so far unresolved functional importance. The microRNA binding site for miR-17 was previously known in species A, B, and C; in this study, we identified it in ten additional species, but not in species K, S, Q, and R. Another interesting finding is the identification of a putative long-distance RNA interaction between the IRES and the 3’ end of the genome. These results together with the now available comprehensive multiple sequence alignment including all 19 pestivirus species, represent a valuable resource for future research and diagnostic purposes.
Ontiveros-Palacios, Nancy; Cooke, Emma; Nawrocki, Eric P.; Triebel, Sandra; Marz, Manja; Rivas, Elena; Griffiths-Jones, Sam; Petrov, Anton I.; Bateman, Alex; Sweeney, Blake
Rfam 15: RNA families database in 2025 Journal Article
In: Nucleic Acids Research, 2025.
Abstract | Links | BibTeX | Tags: database, ncRNAs, RNA structure, RNA-RNA interactions
@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}
}
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.
2024
Triebel, Sandra; Lamkiewicz, Kevin; Ontiveros, Nancy; Sweeney, Blake; Stadler, Peter F.; Petrov, Anton I.; Niepmann, Michael; Marz, Manja
Comprehensive survey of conserved RNA secondary structures in full-genome alignment of Hepatitis C virus Journal Article
In: Scientific Reports, vol. 14, iss. 1, 2024.
Abstract | Links | BibTeX | Tags: evolution, ncRNAs, phylogenetics, RNA structure, RNA-RNA interactions, virus host interaction, viruses
@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}
}
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.
2023
Jakob, Celia; Lovate, Gabriel L.; Desirò, Daniel; Gießler, Lara; Smyth, Redmond Patrick; Marquet, Roland; Lamkiewicz, Kevin; Marz, Manja; Schwemmle, Martin; Bolte, Hardin
Sequential disruption of SPLASH-identified vRNA–vRNA interactions challenges their role in influenza A virus genome packaging Journal Article
In: Nucleic Acids Research, 2023, ISBN: 0305-1048.
Abstract | Links | BibTeX | Tags: RNA-RNA interactions, splash, viruses
@article{nokey_34,
title = {Sequential disruption of SPLASH-identified vRNA–vRNA interactions challenges their role in influenza A virus genome packaging},
author = {Celia Jakob and Gabriel L. Lovate and Daniel Desirò and Lara Gießler and Redmond Patrick Smyth and Roland Marquet and Kevin Lamkiewicz and Manja Marz and Martin Schwemmle and Hardin Bolte},
doi = {10.1093/nar/gkad442},
isbn = {0305-1048},
year = {2023},
date = {2023-07-07},
urldate = {2023-07-07},
journal = {Nucleic Acids Research},
abstract = {A fundamental step in the influenza A virus (IAV) replication cycle is the coordinated packaging of eight distinct genomic RNA segments (i.e. vRNAs) into a viral particle. Although this process is thought to be controlled by specific vRNA–vRNA interactions between the genome segments, few functional interactions have been validated. Recently, a large number of potentially functional vRNA–vRNA interactions have been detected in purified virions using the RNA interactome capture method SPLASH. However, their functional significance in coordinated genome packaging remains largely unclear. Here, we show by systematic mutational analysis that mutant A/SC35M (H7N7) viruses lacking several prominent SPLASH-identified vRNA–vRNA interactions involving the HA segment package the eight genome segments as efficiently as the wild-type virus. We therefore propose that the vRNA–vRNA interactions identified by SPLASH in IAV particles are not necessarily critical for the genome packaging process, leaving the underlying molecular mechanism elusive.},
keywords = {RNA-RNA interactions, splash, viruses},
pubstate = {published},
tppubtype = {article}
}
A fundamental step in the influenza A virus (IAV) replication cycle is the coordinated packaging of eight distinct genomic RNA segments (i.e. vRNAs) into a viral particle. Although this process is thought to be controlled by specific vRNA–vRNA interactions between the genome segments, few functional interactions have been validated. Recently, a large number of potentially functional vRNA–vRNA interactions have been detected in purified virions using the RNA interactome capture method SPLASH. However, their functional significance in coordinated genome packaging remains largely unclear. Here, we show by systematic mutational analysis that mutant A/SC35M (H7N7) viruses lacking several prominent SPLASH-identified vRNA–vRNA interactions involving the HA segment package the eight genome segments as efficiently as the wild-type virus. We therefore propose that the vRNA–vRNA interactions identified by SPLASH in IAV particles are not necessarily critical for the genome packaging process, leaving the underlying molecular mechanism elusive.
2022
Desiro, Daniel
The complexity of packaging mechanisms in segmented RNA viruses PhD Thesis
2022.
Links | BibTeX | Tags: RNA-RNA interactions, viruses
@phdthesis{nokey_38,
title = {The complexity of packaging mechanisms in segmented RNA viruses},
author = {Daniel Desiro},
url = {https://suche.thulb.uni-jena.de/Record/1824169086},
year = {2022},
date = {2022-10-26},
howpublished = {Friedrich-Schiller-Universität Jena},
keywords = {RNA-RNA interactions, viruses},
pubstate = {published},
tppubtype = {phdthesis}
}
Lamkiewicz, Kevin
2022.
Links | BibTeX | Tags: RNA structure, RNA-RNA interactions, viruses
@phdthesis{nokey_36,
title = {RNA secondary structures in RNA viruses: Why viruses would not exist without RNA secondary structures},
author = {Kevin Lamkiewicz},
url = {https://suche.thulb.uni-jena.de/Record/1811938531},
year = {2022},
date = {2022-07-13},
howpublished = {Friedrich-Schiller-Universität Jena},
keywords = {RNA structure, RNA-RNA interactions, viruses},
pubstate = {published},
tppubtype = {phdthesis}
}
2018
Desiro, Daniel; Hölzer, Martin; Ibrahim, Bashar; Marz, Manja
SilentMutations (SIM): a tool for analyzing long-range RNA-RNA interactions in viral genomes and structured RNAs Journal Article
In: Virus Res, vol. 260, pp. 135-141, 2018.
Abstract | Links | BibTeX | Tags: RNA structure, RNA-RNA interactions, software, viruses
@article{Desiro:18,
title = {SilentMutations (SIM): a tool for analyzing long-range RNA-RNA interactions in viral genomes and structured RNAs},
author = {Daniel Desiro and Martin Hölzer and Bashar Ibrahim and Manja Marz},
url = {https://github.com/desiro/silentMutations},
doi = {10.1016/j.virusres.2018.11.005},
year = {2018},
date = {2018-11-12},
urldate = {2018-11-12},
journal = {Virus Res},
volume = {260},
pages = {135-141},
abstract = {A single nucleotide change in the coding region can alter the amino acid sequence of a protein. In consequence, natural or artificial sequence changes in viral RNAs may have various effects not only on protein stability, function and structure but also on viral replication. In recent decades, several tools have been developed to predict the effect of mutations in structured RNAs such as viral genomes or non-coding RNAs. Some tools use multiple point mutations and also take coding regions into account. However, none of these tools was designed to specifically simulate the effect of mutations on viral long-range interactions. Here, we developed SilentMutations (SIM), an easy-to-use tool to analyze the effect of multiple point mutations on the secondary structures of two interacting viral RNAs. The tool can simulate disruptive and compensatory mutants of two interacting single-stranded RNAs. This allows a fast and accurate assessment of key regions potentially involved in functional long-range RNA-RNA interactions and will eventually help virologists and RNA-experts to design appropriate experiments. SIM only requires two interacting single-stranded RNA regions as input. The output is a plain text file containing the most promising mutants and a graphical representation of all interactions. We applied our tool on two experimentally validated influenza A virus and hepatitis C virus interactions and we were able to predict potential double mutants for in vitro validation experiments. The source code and documentation of SIM are freely available at github.com/desiro/silentMutations.},
keywords = {RNA structure, RNA-RNA interactions, software, viruses},
pubstate = {published},
tppubtype = {article}
}
A single nucleotide change in the coding region can alter the amino acid sequence of a protein. In consequence, natural or artificial sequence changes in viral RNAs may have various effects not only on protein stability, function and structure but also on viral replication. In recent decades, several tools have been developed to predict the effect of mutations in structured RNAs such as viral genomes or non-coding RNAs. Some tools use multiple point mutations and also take coding regions into account. However, none of these tools was designed to specifically simulate the effect of mutations on viral long-range interactions. Here, we developed SilentMutations (SIM), an easy-to-use tool to analyze the effect of multiple point mutations on the secondary structures of two interacting viral RNAs. The tool can simulate disruptive and compensatory mutants of two interacting single-stranded RNAs. This allows a fast and accurate assessment of key regions potentially involved in functional long-range RNA-RNA interactions and will eventually help virologists and RNA-experts to design appropriate experiments. SIM only requires two interacting single-stranded RNA regions as input. The output is a plain text file containing the most promising mutants and a graphical representation of all interactions. We applied our tool on two experimentally validated influenza A virus and hepatitis C virus interactions and we were able to predict potential double mutants for in vitro validation experiments. The source code and documentation of SIM are freely available at github.com/desiro/silentMutations.
2016
Madhugiri, Ramakanth; Fricke, Markus; Marz, Manja; Ziebuhr, John
Coronavirus cis-Acting RNA Elements Book Section
In: Coronaviruses, vol. 96, pp. 127–163, Elsevier, 2016.
Abstract | Links | BibTeX | Tags: coronavirus, RNA / transcriptomics, RNA structure, RNA-RNA interactions, viruses
@incollection{Madhugiri:16,
title = {Coronavirus cis-Acting RNA Elements},
author = {Ramakanth Madhugiri and Markus Fricke and Manja Marz and John Ziebuhr},
doi = {10.1016/bs.aivir.2016.08.007},
year = {2016},
date = {2016-09-06},
urldate = {2016-09-06},
booktitle = {Coronaviruses},
volume = {96},
pages = {127--163},
publisher = {Elsevier},
abstract = {Coronaviruses have exceptionally large RNA genomes of approximately 30 kilobases. Genome replication and transcription is mediated by a multisubunit protein complex comprised of more than a dozen virus-encoded proteins. The protein complex is thought to bind specific cis-acting RNA elements primarily located in the 5′- and 3′-terminal genome regions and upstream of the open reading frames located in the 3′-proximal one-third of the genome. Here, we review our current understanding of coronavirus cis-acting RNA elements, focusing on elements required for genome replication and packaging. Recent bioinformatic, biochemical, and genetic studies suggest a previously unknown level of conservation of cis-acting RNA structures among different coronavirus genera and, in some cases, even beyond genus boundaries. Also, there is increasing evidence to suggest that individual cis-acting elements may be part of higher-order RNA structures involving long-range and dynamic RNA–RNA interactions between RNA structural elements separated by thousands of nucleotides in the viral genome. We discuss the structural and functional features of these cis-acting RNA elements and their specific functions in coronavirus RNA synthesis.},
keywords = {coronavirus, RNA / transcriptomics, RNA structure, RNA-RNA interactions, viruses},
pubstate = {published},
tppubtype = {incollection}
}
Coronaviruses have exceptionally large RNA genomes of approximately 30 kilobases. Genome replication and transcription is mediated by a multisubunit protein complex comprised of more than a dozen virus-encoded proteins. The protein complex is thought to bind specific cis-acting RNA elements primarily located in the 5′- and 3′-terminal genome regions and upstream of the open reading frames located in the 3′-proximal one-third of the genome. Here, we review our current understanding of coronavirus cis-acting RNA elements, focusing on elements required for genome replication and packaging. Recent bioinformatic, biochemical, and genetic studies suggest a previously unknown level of conservation of cis-acting RNA structures among different coronavirus genera and, in some cases, even beyond genus boundaries. Also, there is increasing evidence to suggest that individual cis-acting elements may be part of higher-order RNA structures involving long-range and dynamic RNA–RNA interactions between RNA structural elements separated by thousands of nucleotides in the viral genome. We discuss the structural and functional features of these cis-acting RNA elements and their specific functions in coronavirus RNA synthesis.
Fricke, Markus; Marz, Manja
Prediction of conserved long-range RNA-RNA interactions in full viral genomes Journal Article
In: Bioinformatics, vol. 32, no. 19, pp. 2928–2935, 2016.
Abstract | Links | BibTeX | Tags: alignment, RNA / transcriptomics, RNA structure, RNA-RNA interactions, software, viruses
@article{Fricke:16,
title = {Prediction of conserved long-range RNA-RNA interactions in full viral genomes},
author = {Markus Fricke and Manja Marz},
url = {http://www.rna.uni-jena.de/en/supplements/lriscan/},
doi = {10.1093/bioinformatics/btw323},
year = {2016},
date = {2016-06-10},
urldate = {2016-06-10},
journal = {Bioinformatics},
volume = {32},
number = {19},
pages = {2928--2935},
abstract = {Long-range RNA-RNA interactions (LRIs) play an important role in viral replication, however, only a few of these interactions are known and only for a small number of viral species. Up to now, it has been impossible to screen a full viral genome for LRIs experimentally or in silico Most known LRIs are cross-reacting structures (pseudoknots) undetectable by most bioinformatical tools. We present LRIscan, a tool for the LRI prediction in full viral genomes based on a multiple genome alignment. We confirmed 14 out of 16 experimentally known and evolutionary conserved LRIs in genome alignments of HCV, Tombusviruses, Flaviviruses and HIV-1. We provide several promising new interactions, which include compensatory mutations and are highly conserved in all considered viral sequences. Furthermore, we provide reactivity plots highlighting the hot spots of predicted LRIs. Source code and binaries of LRIscan freely available for download at http://www.rna.uni-jena.de/en/supplements/lriscan/, implemented in Ruby/C ++ and supported on Linux and Windows. manja@uni-jena.de Supplementary data are available at Bioinformatics online.},
keywords = {alignment, RNA / transcriptomics, RNA structure, RNA-RNA interactions, software, viruses},
pubstate = {published},
tppubtype = {article}
}
Long-range RNA-RNA interactions (LRIs) play an important role in viral replication, however, only a few of these interactions are known and only for a small number of viral species. Up to now, it has been impossible to screen a full viral genome for LRIs experimentally or in silico Most known LRIs are cross-reacting structures (pseudoknots) undetectable by most bioinformatical tools. We present LRIscan, a tool for the LRI prediction in full viral genomes based on a multiple genome alignment. We confirmed 14 out of 16 experimentally known and evolutionary conserved LRIs in genome alignments of HCV, Tombusviruses, Flaviviruses and HIV-1. We provide several promising new interactions, which include compensatory mutations and are highly conserved in all considered viral sequences. Furthermore, we provide reactivity plots highlighting the hot spots of predicted LRIs. Source code and binaries of LRIscan freely available for download at http://www.rna.uni-jena.de/en/supplements/lriscan/, implemented in Ruby/C ++ and supported on Linux and Windows. manja@uni-jena.de Supplementary data are available at Bioinformatics online.
Fricke, Markus
2016.
Links | BibTeX | Tags: RNA / transcriptomics, RNA structure, RNA-RNA interactions, viruses
@phdthesis{Fricke2016,
title = {RNA structure analysis and conserved long-range RNA-RNA interaction prediction of full viral RNA genomes},
author = {Markus Fricke},
url = {https://suche.thulb.uni-jena.de/Record/865455945},
year = {2016},
date = {2016-01-01},
urldate = {2016-01-01},
howpublished = {Friedrich-Schiller-Universität Jena},
keywords = {RNA / transcriptomics, RNA structure, RNA-RNA interactions, viruses},
pubstate = {published},
tppubtype = {phdthesis}
}
2015
Fricke, Markus; Dünnes, Nadia; Zayas, Margarita; Bartenschlager, Ralf; Niepmann, Michael; Marz, Manja
Conserved RNA secondary structures and long-range interactions in hepatitis C viruses Journal Article
In: RNA, vol. 21, pp. 1219–1232, 2015.
Abstract | Links | BibTeX | Tags: alignment, RNA / transcriptomics, RNA structure, RNA-RNA interactions, viruses
@article{Fricke:15,
title = {Conserved RNA secondary structures and long-range interactions in hepatitis C viruses},
author = {Markus Fricke and Nadia Dünnes and Margarita Zayas and Ralf Bartenschlager and Michael Niepmann and Manja Marz},
doi = {10.1261/rna.049338.114},
year = {2015},
date = {2015-05-11},
urldate = {2015-05-11},
journal = {RNA},
volume = {21},
pages = {1219--1232},
abstract = {Hepatitis C virus (HCV) is a hepatotropic virus with a plus-strand RNA genome of ∼9.600 nt. Due to error-prone replication by its RNA-dependent RNA polymerase (RdRp) residing in nonstructural protein 5B (NS5B), HCV isolates are grouped into seven genotypes with several subtypes. By using whole-genome sequences of 106 HCV isolates and secondary structure alignments of the plus-strand genome and its minus-strand replication intermediate, we established refined secondary structures of the 5' untranslated region (UTR), the cis-acting replication element (CRE) in NS5B, and the 3' UTR. We propose an alternative structure in the 5' UTR, conserved secondary structures of 5B stem-loop (SL)1 and 5BSL2, and four possible structures of the X-tail at the very 3' end of the HCV genome. We predict several previously unknown long-range interactions, most importantly a possible circularization interaction between distinct elements in the 5' and 3' UTR, reminiscent of the cyclization elements of the related flaviviruses. Based on analogy to these viruses, we propose that the 5'-3' UTR base-pairing in the HCV genome might play an important role in viral RNA replication. These results may have important implications for our understanding of the nature of the cis-acting RNA elements in the HCV genome and their possible role in regulating the mutually exclusive processes of viral RNA translation and replication.},
keywords = {alignment, RNA / transcriptomics, RNA structure, RNA-RNA interactions, viruses},
pubstate = {published},
tppubtype = {article}
}
Hepatitis C virus (HCV) is a hepatotropic virus with a plus-strand RNA genome of ∼9.600 nt. Due to error-prone replication by its RNA-dependent RNA polymerase (RdRp) residing in nonstructural protein 5B (NS5B), HCV isolates are grouped into seven genotypes with several subtypes. By using whole-genome sequences of 106 HCV isolates and secondary structure alignments of the plus-strand genome and its minus-strand replication intermediate, we established refined secondary structures of the 5' untranslated region (UTR), the cis-acting replication element (CRE) in NS5B, and the 3' UTR. We propose an alternative structure in the 5' UTR, conserved secondary structures of 5B stem-loop (SL)1 and 5BSL2, and four possible structures of the X-tail at the very 3' end of the HCV genome. We predict several previously unknown long-range interactions, most importantly a possible circularization interaction between distinct elements in the 5' and 3' UTR, reminiscent of the cyclization elements of the related flaviviruses. Based on analogy to these viruses, we propose that the 5'-3' UTR base-pairing in the HCV genome might play an important role in viral RNA replication. These results may have important implications for our understanding of the nature of the cis-acting RNA elements in the HCV genome and their possible role in regulating the mutually exclusive processes of viral RNA translation and replication.
2011
Li, Andrew X; Marz, Manja; Qin, Jing; Reidys, Christian M
RNA-RNA interaction prediction based on multiple sequence alignments Journal Article
In: Bioinformatics, vol. 27, pp. 456–463, 2011.
Abstract | Links | BibTeX | Tags: alignment, evolution, RNA structure, RNA-RNA interactions
@article{Li:11,
title = {RNA-RNA interaction prediction based on multiple sequence alignments},
author = {Andrew X Li and Manja Marz and Jing Qin and Christian M Reidys},
url = {http://www.combinatorics.cn/cbpc/ripalign.html},
doi = {10.1093/bioinformatics/btq659},
year = {2011},
date = {2011-01-01},
urldate = {2011-01-01},
journal = {Bioinformatics},
volume = {27},
pages = {456--463},
abstract = {Many computerized methods for RNA-RNA interaction structure prediction have been developed. Recently, O(N(6)) time and O(N(4)) space dynamic programming algorithms have become available that compute the partition function of RNA-RNA interaction complexes. However, few of these methods incorporate the knowledge concerning related sequences, thus relevant evolutionary information is often neglected from the structure determination. Therefore, it is of considerable practical interest to introduce a method taking into consideration both: thermodynamic stability as well as sequence/structure covariation. We present the a priori folding algorithm ripalign, whose input consists of two (given) multiple sequence alignments (MSA). ripalign outputs (i) the partition function, (ii) base pairing probabilities, (iii) hybrid probabilities and (iv) a set of Boltzmann-sampled suboptimal structures consisting of canonical joint structures that are compatible to the alignments. Compared to the single sequence-pair folding algorithm rip, ripalign requires negligible additional memory resource but offers much better sensitivity and specificity, once alignments of suitable quality are given. ripalign additionally allows to incorporate structure constraints as input parameters. The algorithm described here is implemented in C as part of the rip package.},
keywords = {alignment, evolution, RNA structure, RNA-RNA interactions},
pubstate = {published},
tppubtype = {article}
}
Many computerized methods for RNA-RNA interaction structure prediction have been developed. Recently, O(N(6)) time and O(N(4)) space dynamic programming algorithms have become available that compute the partition function of RNA-RNA interaction complexes. However, few of these methods incorporate the knowledge concerning related sequences, thus relevant evolutionary information is often neglected from the structure determination. Therefore, it is of considerable practical interest to introduce a method taking into consideration both: thermodynamic stability as well as sequence/structure covariation. We present the a priori folding algorithm ripalign, whose input consists of two (given) multiple sequence alignments (MSA). ripalign outputs (i) the partition function, (ii) base pairing probabilities, (iii) hybrid probabilities and (iv) a set of Boltzmann-sampled suboptimal structures consisting of canonical joint structures that are compatible to the alignments. Compared to the single sequence-pair folding algorithm rip, ripalign requires negligible additional memory resource but offers much better sensitivity and specificity, once alignments of suitable quality are given. ripalign additionally allows to incorporate structure constraints as input parameters. The algorithm described here is implemented in C as part of the rip package.