Coupled nucleotide covariations reveal dynamic RNA interaction patterns

Evolutionarily conserved structures in related RNA molecules contain coordi nated variations (covariations) of paired nucleotides, Analysis of covariat ions is a very powerful approach to deduce phylogenetically conserved (i,e. , functional) conformations, including tertiary interactions. Here we discu ss conserved RNA folding pathways that are revealed by covariation patterns . In such pathways, structural requirements for alternative pairings cause some nucleotides to covary with two different partners. Such "coupled" cova riations between three or more nucleotides were found in various types of R NAs, The analysis of coupled covariations can unravel important features of RNA folding dynamics and improve phylogeny reconstruction in some cases, I mportantly, it is necessary to distinguish between multiple covariations de termined by mutually exclusive structures and those determined by tertiary contacts.