Mapping of conserved RNA secondary structures predicts thousands of functional noncoding RNAs in the human genome

• Published in: Nature biotechnology Vol. 23; no. 11; pp. 1383 - 1390
• Main Authors: Stadler, Peter F, Lukasser, Melanie, Hüttenhofer, Alexander, Washietl, Stefan, Hofacker, Ivo L
• Format: Journal Article
• Language: English
• Published: New York, NY Nature 01.11.2005; Nature Publishing Group
• Subjects: Animals; Base Pairing; Base Sequence; Biological and medical sciences; Biotechnology; Chromosome Mapping; Computational Biology - methods; Conservation; Conserved Sequence; Deoxyribonucleic acid; DNA; Fundamental and applied biological sciences. Psychology; Genome, Human; Humans; Introns; Models, Statistical; Molecular and cellular biology; Nucleic Acid Conformation; Phylogeny; Regulatory Elements, Transcriptional; RNA - chemistry; RNA, Messenger - metabolism; RNA, Untranslated - chemistry; Sensitivity and Specificity; Sequence Analysis, DNA; Thermodynamics; Transcription, Genetic; Vertebrates; Human; Conserved sequence; Gene; RNA; Genomics; Non coding sequence; Genome; Secondary structure; Annotation; Comparative study; Protein
• ISSN: 1087-0156; 1546-1696
• DOI: 10.1038/nbt1144

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.