title: Mapping of conserved RNA secondary structures predicts thousands of functional noncoding RNAs in the human genome.
abstract: In contrast to the fairly reliable and complete annotation of the protein coding genes in the human genome, comparable information is lacking for noncoding RNAs (ncRNAs). We present a comparative screen of vertebrate genomes for structural noncoding RNAs, which evaluates conserved genomic DNA sequences for signatures of structural conservation of base-pairing patterns and exceptional thermodynamic stability. We predict more than 30,000 structured RNA elements in the human genome, almost 1,000 of which are conserved across all vertebrates. Roughly a third are found in introns of known genes, a sixth are potential regulatory elements in untranslated regions of protein-coding mRNAs and about half are located far away from any known gene. Only a small fraction of these sequences has been described previously. A comparison with recent tiling array data shows that more than 40% of the predicted structured RNAs overlap with experimentally detected sites of transcription. The widespread conservation of secondary structure points to a large number of functional ncRNAs and cis-acting mRNA structures in the human genome.
authors.affiliation: Institute for Theoretical Chemistry, University of Vienna, Währingerstrasse 17, 1090 Vienna, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Washietl
authors.forename: Ivo L
authors.initials: IL
authors.lastname: Hofacker
authors.forename: Melanie
authors.initials: M
authors.lastname: Lukasser
authors.forename: Alexander
authors.initials: A
authors.lastname: Hüttenhofer
authors.forename: Peter F
authors.initials: PF
authors.lastname: Stadler
mesh_terms: D000818:Animals; D020029:Base Pairing; D001483:Base Sequence; D002874:Chromosome Mapping; D019295:Computational Biology / Q000379:methods; D017124:Conserved Sequence; D015894:Genome, Human; D006801:Humans; D007438:Introns; D015233:Models, Statistical; D009690:Nucleic Acid Conformation; D010802:Phylogeny; D012313:RNA / Q000737:chemistry; D012333:RNA, Messenger / Q000378:metabolism; D022661:RNA, Untranslated / Q000737:chemistry*; D050436:Regulatory Elements, Transcriptional; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA; D013816:Thermodynamics; D014158:Transcription, Genetic
chemical_list: D012333:RNA, Messenger; D022661:RNA, Untranslated; D012313:RNA