IDENTIFICATION OF BASE-TRIPLES IN RNA USING COMPARATIVE SEQUENCE-ANALYSIS

Comparative sequence analysis has proven to be a very efficient tool f or the determination of RNA secondary structure and certain tertiary i nteractions. However, base-triples, an important RNA structural elemen t, cannot be predicted accurately from sequence data. We show here tha t the poor base correlations observed at base-triple positions are the result of two factors. (1) Base covariation is not as strictly requir ed in triples as it is in Watson-Crick pairs. (2) Base-triple structur es are less conserved among homologous molecules. A particularity of k nown triple-helical regions is the presence of multiple base correlati ons that do not reflect direct pairing. We suggest that natural mutati ons in base-triples create structural changes that require compensator y 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-tripl e signal in correlation studies. We evaluated correlations between bas e-pairs and single stranded bases, and correlations between adjacent b ase-pairs. Positions that score well in both analyses are the best tri ple candidates. This procedure correctly identifies triples, or intera ctions very close to the proposed triples, in type I and type II tRNAs and in the group I intron.