Native secondary structure formation in RNA may be a slave to tertiary folding.

Abstract

Implicit in all of the proposed folding mechanisms is the assumption that there are two major structural changes in RNA en route to the native state, starting from an ensemble of unfolded molecules. It is supposed that stable secondary structures form rapidly, perhaps on microsecond time scales. The subsequent assembly leading to tertiary folding takes place by bringing the secondary structural elements together. The resulting kinetics of the assembly of the secondary structural elements is complex because of inherent topological frustration (8). The evidence for the two-step process (reminiscent of framework-like models in protein folding), namely, fast secondary structure formation followed by a slower acquisition of tertiary interactions, came from the folding studies of tRNA (9). In an illuminating paper in this issue of the Proceedings, Wu and Tinoco (10) show that this commonly held picture of …