2009
Jones, Thomas A; Otto, Wolfgang; Marz, Manja; Eddy, Sean R; Stadler, Peter F
A survey of nematode SmY RNAs Journal Article
In: RNA Biol, vol. 6, pp. 5–8, 2009.
Abstract | Links | BibTeX | Tags: alignment, ncRNAs, RNA / transcriptomics, RNA structure, splicing
@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}
}
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.
Ingalls, Todd; Martius, Georg; Marz, Manja; Prohaska, Sonja J.
Converting DNA to music: ComposAlign Proceedings Article
In: Proceedings of the German Conference on Bioinformatics (GCB 2009), pp. 93-104, 2009.
Abstract | Links | BibTeX | Tags: alignment
@inproceedings{Ingalls:09,
title = {Converting DNA to music: ComposAlign},
author = {Todd Ingalls and Georg Martius and Manja Marz and Sonja J. Prohaska},
url = {https://dl.gi.de/handle/20.500.12116/20313},
year = {2009},
date = {2009-01-01},
urldate = {2009-01-01},
booktitle = {Proceedings of the German Conference on Bioinformatics (GCB 2009)},
volume = {P-157},
pages = {93-104},
series = {GI Lecture Notes in Informatics},
abstract = {Alignments are part of the most important data type in the field of comparative genomics. They can be abstracted to a character matrix derived from aligned sequences. A variety of biological questions forces the researcher to inspect these alignments. Our tool, called COMPOSALIGN, was developed to sonify large scale genomic data. The resulting musical composition is based on COMMON MUSIC and allows the mapping of genes to motifs and species to instruments. It enables the researcher to listen to the musical representation of the genome-wide alignment and contrasts a bioinformatician's sight-oriented work at the computer.},
keywords = {alignment},
pubstate = {published},
tppubtype = {inproceedings}
}
Alignments are part of the most important data type in the field of comparative genomics. They can be abstracted to a character matrix derived from aligned sequences. A variety of biological questions forces the researcher to inspect these alignments. Our tool, called COMPOSALIGN, was developed to sonify large scale genomic data. The resulting musical composition is based on COMMON MUSIC and allows the mapping of genes to motifs and species to instruments. It enables the researcher to listen to the musical representation of the genome-wide alignment and contrasts a bioinformatician's sight-oriented work at the computer.
2008
Marz, Manja; Kirsten, Toralf; Stadler, Peter F
Evolution of spliceosomal snRNA genes in metazoan animals Journal Article
In: J Mol Evol, vol. 67, pp. 594–607, 2008.
Abstract | Links | BibTeX | Tags: evolution, insects, ncRNAs, RNA structure, splicing
@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}
}
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.
Marz, Manja; Mosig, Axel; Stadler, Bärbel M R; Stadler, Peter F
U7 snRNAs: a computational survey Journal Article
In: Genomics Proteomics Bioinformatics, vol. 5, no. 3-4, pp. 187–195, 2008.
Abstract | Links | BibTeX | Tags: evolution, insects, ncRNAs, RNA structure
@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}
}
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.
Gruber, Andreas R; Koper-Emde, Dorota; Marz, Manja; Tafer, Hakim; Bernhart, Stephan; Obernosterer, Gregor; Mosig, Axel; Hofacker, Ivo L; Stadler, Peter F; Benecke, Bernd-Joachim
Invertebrate 7SK snRNAs Journal Article
In: J Mol Evol, vol. 66, pp. 107–115, 2008.
Abstract | Links | BibTeX | Tags: evolution, ncRNAs
@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}
}
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.
2007
Washietl, Stefan; Pedersen, Jakob S; Korbel, Jan O; Stocsits, Claudia; Gruber, Andreas R; Hackermüller, Jörg; Hertel, Jana; Lindemeyer, Manja; Reiche, Kristin; Tanzer, Andrea; Ucla, Catherine; Wyss, Carine; Antonarakis, Stylianos E; Denoeud, France; Lagarde, Julien; Drenkow, Jorg; Kapranov, Philipp; Gingeras, Thomas R; Guigó, Roderic; Snyder, Michael; Gerstein, Mark B; Reymond, Alexandre; Hofacker, Ivo L; Stadler, Peter F
Structured RNAs in the ENCODE selected regions of the human genome Journal Article
In: Genome Res, vol. 17, pp. 852–864, 2007.
Abstract | Links | BibTeX | Tags: annotation, evolution, ncRNAs, RNA structure
@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}
}
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%).
2006
Hertel, Jana; Lindemeyer, Manja; Missal, Kristin; Fried, Claudia; Tanzer, Andrea; Flamm, Christoph; Hofacker, Ivo L.; Stadler, Peter F.; & 2005, Students Bioinformatics Computer Labs 2004
The expansion of the metazoan microRNA repertoire Journal Article
In: BMC Genomics, vol. 7, pp. 25, 2006.
Abstract | Links | BibTeX | Tags: ncRNAs, phylogenetics
@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}
}
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.