Comparative analysis of structured RNAs in S. cerevisiae indicates a multitude of different functions

BackgroundNon-coding RNAs (ncRNAs) are an emerging focus for both computational analysis and experimental research, resulting in a growing number of novel, non-protein coding transcripts with often unknown functions. Whole genome screens in higher eukaryotes, for example, provided evidence for a surprisingly large number of ncRNAs. To supplement these searches, we performed a computational analysis of seven yeast species and searched for new ncRNAs and RNA motifs.ResultsA comparative analysis of the genomes of seven yeast species yielded roughly 2800 genomic loci that showed the hallmarks of evolutionary conserved RNA secondary structures. A total of 74% of these regions overlapped with annotated non-coding or coding genes in yeast. Coding sequences that carry predicted structured RNA elements belong to a limited number of groups with common functions, suggesting that these RNA elements are involved in post-transcriptional regulation and/or cellular localization. About 700 conserved RNA structures were found outside annotated coding sequences and known ncRNA genes. Many of these predicted elements overlapped with UTR regions of particular classes of protein coding genes. In addition, a number of RNA elements overlapped with previously characterized antisense transcripts. Transcription of about 120 predicted elements located in promoter regions and other, previously un-annotated, intergenic regions was supported by tiling array experiments, ESTs, or SAGE data.ConclusionOur computational predictions strongly suggest that yeasts harbor a substantial pool of several hundred novel ncRNAs. In addition, we describe a large number of RNA structures in coding sequences and also within antisense transcripts that were previously characterized using tiling arrays.

[1]  K. Nieselt,et al.  Open reading frames provide a rich pool of potential natural antisense transcripts in fungal genomes , 2005, Nucleic acids research.

[2]  C. Jacq,et al.  In Yeast, the 3′ Untranslated Region or the Presequence ofATM1 Is Required for the Exclusive Localization of Its mRNA to the Vicinity of Mitochondria , 2000, Molecular and Cellular Biology.

[3]  S. Eddy,et al.  A computational screen for methylation guide snoRNAs in yeast. , 1999, Science.

[4]  Ron Shamir,et al.  A catalog of stability-associated sequence elements in 3' UTRs of yeast mRNAs , 2005, Genome Biology.

[5]  Elena Rivas,et al.  Noncoding RNA gene detection using comparative sequence analysis , 2001, BMC Bioinformatics.

[6]  Sean R. Eddy,et al.  Rfam: an RNA family database , 2003, Nucleic Acids Res..

[7]  C. Gissi,et al.  Untranslated regions of mRNAs , 2002, Genome Biology.

[8]  Xiaoqiu Huang,et al.  Over 20% of human transcripts might form sense-antisense pairs. , 2004, Nucleic acids research.

[9]  Graydon B. Gonsalvez,et al.  RNA localization in yeast: moving towards a mechanism , 2005, Biology of the cell.

[10]  E. Mauceli,et al.  The genome sequence of the filamentous fungus Neurospora crassa , 2003, Nature.

[11]  Kimberly Van Auken,et al.  WormBase: a multi-species resource for nematode biology and genomics , 2004, Nucleic Acids Res..

[12]  K. Wassarman,et al.  A highly conserved 6S RNA structure is required for regulation of transcription , 2005, Nature Structural &Molecular Biology.

[13]  Terrence S. Furey,et al.  The UCSC Genome Browser Database: update 2006 , 2005, Nucleic Acids Res..

[14]  C. Burge,et al.  Widespread selection for local RNA secondary structure in coding regions of bacterial genes. , 2003, Genome research.

[15]  D. Monté,et al.  H19 mRNA-like Noncoding RNA Promotes Breast Cancer Cell Proliferation through Positive Control by E2F1* , 2005, Journal of Biological Chemistry.

[16]  Dmitry A. Samarsky,et al.  Characterization of three new snRNAs from Saccharomyces cerevisiae: snR34, snR35 and snR36 , 1995, Nucleic Acids Res..

[17]  Gene Ontology Consortium.  The Gene Ontology (GO) database and informatics resource , 2003 .

[18]  E. Myers,et al.  Basic local alignment search tool. , 1990, Journal of molecular biology.

[19]  I. Longden,et al.  EMBOSS: the European Molecular Biology Open Software Suite. , 2000, Trends in genetics : TIG.

[20]  Yi Zhao,et al.  NONCODE: an integrated knowledge database of non-coding RNAs , 2004, Nucleic Acids Res..

[21]  Liang-Hu Qu,et al.  Seven Novel Methylation Guide Small Nucleolar RNAs Are Processed from a Common Polycistronic Transcript by Rat1p and RNase III in Yeast , 1999, Molecular and Cellular Biology.

[22]  S. Eddy,et al.  Computational identification of non-coding RNAs in Saccharomyces cerevisiae by comparative genomics. , 2003, Nucleic acids research.

[23]  D. Kerrigan,et al.  Structure and function analysis of the poliovirus cis-acting replication element (CRE). , 2003, RNA.

[24]  C. Jacq,et al.  The role of the 3' untranslated region in mRNA sorting to the vicinity of mitochondria is conserved from yeast to human cells. , 2003, Molecular biology of the cell.

[25]  M. Hentze,et al.  Molecular control of vertebrate iron metabolism: mRNA-based regulatory circuits operated by iron, nitric oxide, and oxidative stress. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[26]  P. Brown,et al.  Genome-wide analysis of mRNA lengths in Saccharomyces cerevisiae , 2003, Genome Biology.

[27]  W. J. Kent,et al.  BLAT--the BLAST-like alignment tool. , 2002, Genome research.

[28]  D. Lipman,et al.  Improved tools for biological sequence comparison. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[29]  Brian S. Clark,et al.  The Evf-2 noncoding RNA is transcribed from the Dlx-5/6 ultraconserved region and functions as a Dlx-2 transcriptional coactivator. , 2006, Genes & development.

[30]  Fred Winston,et al.  in Saccharomyces cerevisiae , 2005 .

[31]  J. Maizel,et al.  Extensive sequence-specific information throughout the CAR/RRE, the target sequence of the human immunodeficiency virus type 1 Rev protein , 1992, Journal of virology.

[32]  István Miklós,et al.  Statistical evidence for conserved, local secondary structure in the coding regions of eukaryotic mRNAs and pre-mRNAs , 2005, Nucleic acids research.

[33]  S. Eddy,et al.  Computational identification of noncoding RNAs in E. coli by comparative genomics , 2001, Current Biology.

[34]  Yoshihide Hayashizaki,et al.  Antisense transcripts with FANTOM2 clone set and their implications for gene regulation. , 2003, Genome research.

[35]  C. Ball,et al.  Saccharomyces Genome Database. , 2002, Methods in enzymology.

[36]  S. Lewis,et al.  The generic genome browser: a building block for a model organism system database. , 2002, Genome research.

[37]  B. Barrell,et al.  Life with 6000 Genes , 1996, Science.

[38]  E. R. Gavis,et al.  Overlapping but distinct RNA elements control repression and activation of nanos translation. , 2000, Molecular cell.

[39]  M. Ares,et al.  Accumulation of unstable promoter-associated transcripts upon loss of the nuclear exosome subunit Rrp6p in Saccharomyces cerevisiae. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[40]  David Haussler,et al.  Identification and Classification of Conserved RNA Secondary Structures in the Human Genome , 2006, PLoS Comput. Biol..

[41]  J. Goodrich,et al.  The SINE-encoded mouse B2 RNA represses mRNA transcription in response to heat shock , 2004, Nature Structural &Molecular Biology.

[42]  C. Carles,et al.  Selective Targeting and Inhibition of Yeast RNA Polymerase II by RNA Aptamers* , 1997, The Journal of Biological Chemistry.

[43]  Jason R. Swedlow,et al.  Actin-dependent localization of an RNA encoding a cell-fate determinant in yeast , 1997, Nature.

[44]  C. Chin,et al.  Global identification of noncoding RNAs in Saccharomyces cerevisiae by modulating an essential RNA processing pathway. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[45]  Celso A. Espinoza,et al.  B2 RNA binds directly to RNA polymerase II to repress transcript synthesis , 2004, Nature Structural &Molecular Biology.

[46]  Eli Eisenberg,et al.  Evidence for abundant transcription of non-coding regions in the Saccharomyces cerevisiae genome , 2005, BMC Genomics.

[47]  Masaru Tomita,et al.  Identification and expression analysis of putative mRNA‐like non‐coding RNA in Drosophila , 2005, Genes to cells : devoted to molecular & cellular mechanisms.

[48]  Fred Winston,et al.  Intergenic transcription is required to repress the Saccharomyces cerevisiae SER3 gene , 2004, Nature.

[49]  Wolfgang Huber,et al.  A high-resolution map of transcription in the yeast genome. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[50]  C. Jacq,et al.  In Saccharomyces cerevisiae, ATP2 mRNA sorting to the vicinity of mitochondria is essential for respiratory function , 2002, The EMBO journal.

[51]  C. Gissi,et al.  Structural and functional features of eukaryotic mRNA untranslated regions. , 2001, Gene.

[52]  Ji Huang,et al.  [Serial analysis of gene expression]. , 2002, Yi chuan = Hereditas.

[53]  Peter F Stadler,et al.  Fast and reliable prediction of noncoding RNAs , 2005, Proc. Natl. Acad. Sci. USA.

[54]  E. Wimmer,et al.  A segment of the 5' nontranslated region of encephalomyocarditis virus RNA directs internal entry of ribosomes during in vitro translation , 1988, Journal of virology.

[55]  Wayne A. Decatur,et al.  Genome-wide searching for pseudouridylation guide snoRNAs: analysis of the Saccharomyces cerevisiae genome. , 2004, Nucleic acids research.

[56]  C. Jacq,et al.  Long mRNAs coding for yeast mitochondrial proteins of prokaryotic origin preferentially localize to the vicinity of mitochondria , 2003, Genome Biology.

[57]  W. L. Ruzzo,et al.  6S RNA is a widespread regulator of eubacterial RNA polymerase that resembles an open promoter. , 2005, RNA.

[58]  D. Haussler,et al.  Aligning multiple genomic sequences with the threaded blockset aligner. , 2004, Genome research.

[59]  C. Pleij,et al.  Structural motifs in the RNA encoded by the early nodulation gene enod40 of soybean. , 2003, Nucleic acids research.

[60]  R. Lanz,et al.  Distinct RNA motifs are important for coactivation of steroid hormone receptors by steroid receptor RNA activator (SRA) , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[61]  I. Hofacker,et al.  Consensus folding of aligned sequences as a new measure for the detection of functional RNAs by comparative genomics. , 2004, Journal of molecular biology.

[62]  Nicola J. Rinaldi,et al.  Transcriptional regulatory code of a eukaryotic genome , 2004, Nature.

[63]  K. Nasmyth,et al.  Mating type switching in yeast controlled by asymmetric localization of ASH1 mRNA. , 1997, Science.