Publications

@article{Marz:10,

title = {Temperature-dependent structural variability of RNAs: spliced leader RNAs and their evolutionary history},

author = {Manja Marz and Nathalie Vanzo and Peter F Stadler},

doi = {10.1142/S0219720010004525},

year  = {2010},

date = {2010-09-14},

urldate = {2010-01-01},

journal = {J Bioinform Comput Biol},

volume = {8},

number = {1},

pages = {1--17},

abstract = {The structures attained by RNA molecules depend not only on their sequence but also on environmental parameters such as their temperature. So far, this effect has been largely neglected in bioinformatics studies. Here, we show that structural comparisons can be facilitated and more coherent structural models can be obtained when differences in environmental parameters are taken into account. We re-evaluate the secondary structures of the spliced leader (SL) RNAs from the seven eukaryotic phyla in which SL RNA trans-splicing has been described. Adjusting structure prediction to the natural growth temperatures and considering energetically similar secondary structures, we observe striking similarities among Euglenida, Kinetoplastida, Dinophyceae, Cnidaria, Rotifera, Nematoda, Platyhelminthes, and Tunicata that cannot be explained easily by the independent innovation of SL RNAs in each of these phyla. Supplementary Table is available at http://www.worldscinet.com/jbcb/.},

keywords = {evolution, RNA structure, splicing},

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 and 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}

}