Early events in RNA folding

We describe a conceptual framework for understanding the way large RNA mole cules fold based on the notion that their free-energy landscape is rugged. A key prediction of our theory is that RNA folding can be described by the kinetic partitioning mechanism (KPM). According to KPM a small fraction of molecules folds rapidly to the native state whereas the remaining fraction is kinetically trapped in a low free-energy non-native state. This model pr ovides a unified description of the way RNA and proteins fold. Single-molec ule experiments on Tetrahymena ribozyme, which directly validate our theory , are analyzed using KPM. We also describe the earliest events that occur o n microsecond time scales in RNA folding. These must involve collapse of RN A molecules that are mediated by counterion-condensation. Estimates of time scales for the initial events in RNA folding are provided for the Tetrahym ena ribozyme.