Identification of putative noncoding RNAs among the RIKEN mouse full-length cDNA collection.

With the sequencing and annotation of genomes and transcriptomes of several eukaryotes, the importance of noncoding RNA (ncRNA)-RNA molecules that are not translated to protein products-has become more evident. A subclass of ncRNA transcripts are encoded by highly regulated, multi-exon, transcriptional units, are processed like typical protein-coding mRNAs and are increasingly implicated in regulation of many cellular functions in eukaryotes. This study describes the identification of candidate functional ncRNAs from among the RIKEN mouse full-length cDNA collection, which contains 60,770 sequences, by using a systematic computational filtering approach. We initially searched for previously reported ncRNAs and found nine murine ncRNAs and homologs of several previously described nonmouse ncRNAs. Through our computational approach to filter artifact-free clones that lack protein coding potential, we extracted 4280 transcripts as the largest-candidate set. Many clones in the set had EST hits, potential CpG islands surrounding the transcription start sites, and homologies with the human genome. This implies that many candidates are indeed transcribed in a regulated manner. Our results demonstrate that ncRNAs are a major functional subclass of processed transcripts in mammals.

[1]  M. Frommer,et al.  CpG islands in vertebrate genomes. , 1987, Journal of molecular biology.

[2]  W. Pearson Searching protein sequence libraries: comparison of the sensitivity and selectivity of the Smith-Waterman and FASTA algorithms. , 1991, Genomics.

[3]  J. Merlie,et al.  A novel synapse-associated noncoding RNA , 1994, Molecular and cellular biology.

[4]  P. Scambler,et al.  Identification of a novel transcript disrupted by a balanced translocation associated with DiGeorge syndrome. , 1996, American journal of human genetics.

[5]  K. Davies,et al.  adapt33, a novel oxidant-inducible RNA from hamster HA-1 cells. , 1996, Archives of biochemistry and biophysics.

[6]  J. Steitz,et al.  A mammalian gene with introns instead of exons generating stable RNA products , 1996, Nature.

[7]  U. Francke,et al.  An imprinted mouse transcript homologous to the human imprinted in Prader-Willi syndrome (IPW) gene. , 1997, Human molecular genetics.

[8]  S. Karlin,et al.  Prediction of complete gene structures in human genomic DNA. , 1997, Journal of molecular biology.

[9]  R. Siliciano,et al.  The human NTT gene: identification of a novel 17-kb noncoding nuclear RNA expressed in activated CD4+ T cells. , 1997, Genomics.

[10]  M. Bortolin,et al.  Human U19 intron-encoded snoRNA is processed from a long primary transcript that possesses little potential for protein coding. , 1998, RNA.

[11]  W. Filipowicz,et al.  The Host Gene for Intronic U17 Small Nucleolar RNAs in Mammals Has No Protein-Coding Potential and Is a Member of the 5′-Terminal Oligopyrimidine Gene Family , 1998, Molecular and Cellular Biology.

[12]  J. Steitz,et al.  Classification of gas5 as a Multi-Small-Nucleolar-RNA (snoRNA) Host Gene and a Member of the 5′-Terminal Oligopyrimidine Gene Family Reveals Common Features of snoRNA Host Genes , 1998, Molecular and Cellular Biology.

[13]  C. Chen,et al.  A new structure for the murine Xist gene and its relationship to chromosome choice/counting during X-chromosome inactivation. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[14]  H. Himmelbauer,et al.  Identification and characterization of G90, a novel mouse RNA that lacks an extensive open reading frame. , 1999, Gene.

[15]  D. J. Driscoll,et al.  A maternally methylated CpG island in KvLQT1 is associated with an antisense paternal transcript and loss of imprinting in Beckwith-Wiedemann syndrome. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[16]  L. Hurst,et al.  Molecular evolutionary evidence that H19 mRNA is functional. , 1999, Trends in genetics : TIG.

[17]  Phillip D. Zamore,et al.  RNA Interference , 2000, Science.

[18]  Maciej Szymanski,et al.  Non-coding, mRNA-like RNAs database Y2K , 2000, Nucleic Acids Res..

[19]  T B Nesterova,et al.  Characterization of the genomic Xist locus in rodents reveals conservation of overall gene structure and tandem repeats but rapid evolution of unique sequence. , 2001, Genome research.

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

[21]  T. Bliss,et al.  Ntab, a novel non-coding RNA abundantly expressed in rat brain , 2001, Neuroscience.

[22]  P J Green,et al.  Identification and analysis of Arabidopsis expressed sequence tags characteristic of non-coding RNAs. , 2001, Plant physiology.

[23]  H. Margalit,et al.  Novel small RNA-encoding genes in the intergenic regions of Escherichia coli , 2001, Current Biology.

[24]  W. Tam Identification and characterization of human BIC, a gene on chromosome 21 that encodes a noncoding RNA. , 2001, Gene.

[25]  S. Morita,et al.  Identification of a new imprinted gene, Rian, on mouse chromosome 12 by fluorescent differential display screening. , 2001, Journal of biochemistry.

[26]  L. Lim,et al.  An Abundant Class of Tiny RNAs with Probable Regulatory Roles in Caenorhabditis elegans , 2001, Science.

[27]  P. Sharp,et al.  RNA interference--2001. , 2001, Genes & development.

[28]  G. Storz,et al.  Identification of novel small RNAs using comparative genomics and microarrays. , 2001, Genes & development.

[29]  S. Eddy Computational Genomics of Noncoding RNA Genes , 2002, Cell.

[30]  D. Barlow,et al.  Quantitative genetics: Turning up the heat on QTL mapping , 2002, Nature Reviews Genetics.

[31]  A. Hüttenhofer,et al.  Identification of 86 candidates for small non-messenger RNAs from the archaeon Archaeoglobus fulgidus , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[32]  A. Iacoangeli,et al.  Poly(A)-binding protein is associated with neuronal BC1 and BC200 ribonucleoprotein particles. , 2002, Journal of molecular biology.

[33]  S. Hirose,et al.  Identification of a Novel Osteoblastic Gene, Inducible by C-type Natriuretic Peptide, Whose Transcript Might Function in Mineralization as a Noncoding RNA , 2002, Calcified Tissue International.

[34]  K. Wassarman Small RNAs in Bacteria Diverse Regulators of Gene Expression in Response to Environmental Changes , 2002, Cell.

[35]  Daiya Takai,et al.  Comprehensive analysis of CpG islands in human chromosomes 21 and 22 , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[36]  J. Squire,et al.  Identification of a novel gene NCRMS on chromosome 12q21 with differential expression between Rhabdomyosarcoma subtypes , 2002, Oncogene.

[37]  E. Birney,et al.  Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs , 2002, Nature.

[38]  Zheng Yuan,et al.  The mouse secretome: functional classification of the proteins secreted into the extracellular environment. , 2003, Genome research.

[39]  Y. Hayashizaki,et al.  Systematic expression profiling of the mouse transcriptome using RIKEN cDNA microarrays. , 2003, Genome research.

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

[41]  Paul Denny,et al.  A comprehensive transcript map of the mouse Gnas imprinted complex. , 2003, Genome research.