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Mechanism of RNA Double Helix-Propagation at Atomic Resolution

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journal contribution
posted on 05.03.2009, 00:00 by Srividya Mohan, Chiaolong Hsiao, Halena VanDeusen, Ryan Gallagher, Eric Krohn, Benson Kalahar, Roger M. Wartell, Loren Dean Williams
The conversion of a nucleic acid from single strands to double strands is thought to involve slow nucleation followed by fast double-strand propagation. Here, for RNA double-strand propagation, we propose an atomic resolution reaction mechanism. This mechanism, called the stack-ratchet, is based on data-mining of three-dimensional structures and on available thermodynamic information. The stack-ratchet mechanism extends and adds detail to the classic zipper model proposed by Porschke (Porschke, D. Biophysical Chemistry 1974, 2, pp. 97−101). Porschke’s zipper model describes the addition of a base pair to a nucleated helix in terms of a single type of elementary reaction; a concerted process in which the two bases, one from each strand, participate in the transition state. In the stack-ratchet mechanism proposed here a net base-pairing step consists of two elementary reactions. Motions of only one strand are required to achieve a given transition state. One elementary reaction preorganizes and stacks the 3′ single-strand, driven by base−base stacking interactions. A second elementary reaction stacks the 5′ strand and pairs it with the preorganized 3′ strand. In the stack-ratchet mechanism, a variable length 3′ stack leads the single-strand/double-strand junction. The stack-ratchet mechanism is not a two-state process. A base can be (i) unstacked and unpaired, (ii) stacked and paired, or (ii) stacked and unpaired (only on the 3′ strand). The data suggests that helices of DNA and of RNA do not propagate by similar mechanisms.