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22 Predicting RNA Secondary Structure

David H. Mathews, Susan J. Schroeder, Douglas H. Turner, Michael Zuker


In the “RNA World” hypothesis, RNA is the molecule responsible for both catalysis and transmission of genetic information. In various ways, RNA still performs these functions. To function as more than an information carrier, RNA must fold into specific three-dimensional shapes. Determining the canonical base-pairing, i.e., secondary structure, of RNA is the cornerstone for predicting three-dimensional structure (Turner et al. 1988; Chapter 23) because helices in RNA are usually stronger than the tertiary interactions that connect elements of secondary structure (Crothers et al. 1974; Banerjee et al. 1993; Jaeger et al. 1993; Laing and Draper 1994; Tinoco and Bustamante 1999).

The folding of RNA may be determined by kinetics or thermodynamics or both. The observations that many known RNAs can be renatured outside the cell and that the secondary structures of domains of less than 500 nucleotides can be predicted with about 73% accuracy from known thermodynamics (Mathews et al. 1999a, 2004a) suggest that their functional folds are largely determined by thermodynamics. Thus, thermodynamics can be a useful tool for interpreting in vitro experiments of RNA evolution and providing insight into the early stages of natural selection. Folding of an RNA chain is a unimolecular reaction:(1)U⇌F   K=[F]/[U]=e-ΔGo/RT

Here, K is the equilibrium constant giving the ratio of concentrations for folded, F, and unfolded, U, species at equilibrium; Δ G° is the standard free-energy difference between F and U; R is the gas constant, 1.987 cal K−1 mole−1; and T is the temperature in kelvins. The challenge of predicting secondary...

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