Identification of base-triples in RNA using comparative sequence analysis.
Comparative sequence analysis has proven to be a very efficient tool for the determination of RNA secondary structure and certain tertiary interactions. However, base-triples, an important RNA structural element, cannot be predicted accurately from sequence data. We show here that the poor base correlations observed at base-triple positions are the result of two factors. (1) Base covariation is not as strictly required in triples as it is in Watson-Crick pairs. (2) Base-triple structures are less conserved among homologous molecules. A particularity of known triple-helical regions is the presence of multiple base correlations that do not reflect direct pairing. We suggest that natural mutations in base-triples create structural changes that require compensatory mutations in adjacent base-pairs and triples to maintain the triple-helix conformation. On the basis of these observations, we devised two new measures of association that significantly enhance the base-triple signal in correlation studies. We evaluated correlations between base-pairs and single stranded bases, and correlations between adjacent base-pairs. Positions that score well in both analyses are the best triple candidates. This procedure correctly identifies triples, or interactions very close to the proposed triples, in type I and type II tRNAs and in the group I intron.
Gautheret
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Department of Molecular, Cellular and Developmental Biology, Universityof Colorado, Boulder 80309-0347, USA.
Damberger
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Gutell
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D001482:Base Composition; D001483:Base Sequence; D004926:Escherichia coli / Q000378:metabolism; D006860:Hydrogen Bonding; D007438:Introns; D008958:Models, Molecular; D015233:Models, Statistical; D009690:Nucleic Acid Conformation; D012313:RNA / Q000737:chemistry*; D012349:RNA, Transfer, Asp / Q000737:chemistry; D012351:RNA, Transfer, Gln / Q000737:chemistry; D012360:RNA, Transfer, Phe / Q000737:chemistry; D012362:RNA, Transfer, Ser / Q000737:chemistry; D012441:Saccharomyces cerevisiae / Q000378:metabolism
D012349:RNA, Transfer, Asp; D012351:RNA, Transfer, Gln; D012360:RNA, Transfer, Phe; D012362:RNA, Transfer, Ser; D012313:RNA