The jerky and knotty dynamics of RNA

RNA is known to exhibit a jerky dynamics, as intramolecular thermal motion, on < 0.1 mu s time scales, is punctuated by infrequent structural rearrangements on much longer time scales, i.e. from > 10 mu s up to a few minutes or even hours. These rare stochastic events correspond to the formation or dissociation of entire stems through cooperative base pairing/unpairing transitions. Such a clear separation of time scales in RNA dynamics has made it possible to implement coarse grained RNA simulations, which predict RNA folding and unfolding pathways including kinetically trapped structures on biologically relevant time scales of seconds to minutes. RNA folding simulations also enable to predict the formation of pseudoknots, that is, helices interior to loops, which mechanically restrain the relative orientations of other non-nested helices. But beyond static structural constraints, pseudoknots can also strongly affect the folding and unfolding dynamics of RNA. as the order by which successive helices are formed and dissociated can lead to topologically blocked transition intermediates. The resulting knotty dynamics can enhance the stability of RNA switches, improve the efficacy of co-transcriptional folding pathways and lead to unusual self-assembly properties of RNA. (c) 2009 Elsevier Inc. All rights reserved.