Changbong Hyeon and D. Thirumalai
We show that the folding rates (kFs) of RNA are determined by N, the number of nucleotides. By assuming that the distribution of free-energy barriers separating the folded and the unfolded states is Gaussian, which follows from central limit theorem arguments and polymer physics concepts, we show that . Remarkably, the theory fits experimental rates spanning over 7 orders of magnitude with . Our finding suggests that the speed limit of RNA folding is ∼1 ms, just as it is in the folding of globular proteins. RNA molecules are evolved biopolymers whose folding has attracted a great deal of attention because of the crucial role they play in a number of cellular functions. The slightly branched polymeric nature of RNA implies that the shapes, relaxation dynamics, and even their folding rates must depend on N. In support of this assertion, it has been shown that the radius of gyration of the folded states, obtained with the use of data available in the Protein Data Bank, scales as Å, where the Flory exponent ν varies from 0.33 to 0.40. Although this result is expected from the perspective of polymer physics, it is surprising from the viewpoint of structural biology because one might argue that the sequence and complexity of secondary and tertiary structure organization could lead to substantial deviations from the predictions based on Flory-like theory. Here, we show that the folding rates, kFs, of RNA are also primarily determined by N, thus adding to the growing evidence that it is possible to understand RNA folding by using polymer physics principles.
DOI
Journal: Biophysical Journal
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