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PMID: 15665081 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Fast and reliable prediction of noncoding RNAs.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 102 ·No. 7 ·2005-02-15 ·Pages 2454-9

Washietl S, Hofacker IL, Stadler PF

Abstract

We report an efficient method for detecting functional RNAs. The approach, which combines comparative sequence analysis and structure prediction, already has yielded excellent results for a small number of aligned sequences and is suitable for large-scale genomic screens. It consists of two basic components: (i) a measure for RNA secondary structure conservation based on computing a consensus secondary structure, and (ii) a measure for thermodynamic stability, which, in the spirit of a z score, is normalized with respect to both sequence length and base composition but can be calculated without sampling from shuffled sequences. Functional RNA secondary structures can be identified in multiple sequence alignments with high sensitivity and high specificity. We demonstrate that this approach is not only much more accurate than previous methods but also significantly faster. The method is implemented in the program rnaz, which can be downloaded from www.tbi.univie.ac.at/~wash/RNAz. We screened all alignments of length n > or = 50 in the Comparative Regulatory Genomics database, which compiles conserved noncoding elements in upstream regions of orthologous genes from human, mouse, rat, Fugu, and zebrafish. We recovered all of the known noncoding RNAs and cis-acting elements with high significance and found compelling evidence for many other conserved RNA secondary structures not described so far to our knowledge.

MeSH Terms
Algorithms Databases, Nucleic Acid Nucleic Acid Conformation RNA Stability RNA, Untranslated/chemistry,genetics Sequence Alignment/statistics & numerical data Software Thermodynamics
Chemicals
RNA, Untranslated
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Washietl Stefan
Department of Theoretical Chemistry and Structural Biology, University of Vienna, Währingerstrasse 17, A-1090 Wien, Austria.
Hofacker Ivo L
Stadler Peter F
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0409169102
Published
2005-02-15
Epub
2005-00-21
Pages
2454-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC548974
Subset
IM
Corrections
CommentIn
PMID: 15703286
External Links
PubMed source DOI: 10.1073/pnas.0409169102 PMC Full Text View journal details
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