Nature Biotechnology 23, 1383 - 1390 (2005)
Published online: 4 November 2005; | doi:10.1038/nbt1144
Mapping of conserved RNA secondary structures predicts thousands of functional noncoding RNAs in the human genomeStefan Washietl1, Ivo L Hofacker1, Melanie Lukasser2, Alexander Hüttenhofer2
& Peter F Stadler3, 41
Institute for Theoretical Chemistry, University of Vienna, Währingerstrasse 17, 1090 Vienna, Austria. 2
Division of Genomics and RNomics, Innsbruck Medical University-Biocenter, Fritz-Pregl-Strasse 3, 6020 Innsbruck, Austria. 3
Department of Computer Science and Interdisciplinary Center of Bioinformatics, University of Leipzig, Härtelstrasse 16-18, D-04107, Leipzig, Germany. 4
Santa Fe Institute, 1399 Hyde Park Rd., Santa Fe, New Mexico 87501, USA.
Correspondence should be addressed to Peter F Stadler studla@bioinf.uni-leipzig.de 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.
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