Methods for Predicting RNA Secondary Structure

Abstract

The formation of RNA structure is a hierarchical process: the secondary structure builds up by thermodynamically favorable stacks of base pairs (helix formation) and unfavorable loops (non-Watson–Crick base pairs; hairpin, internal, and bulge loops; junctions). The tertiary structure folds on top of the thermodynamically optimal or close-to-optimal secondary structure by formation of pseudoknots, base triples, and/or stacking of helices. In this chapter, we will concentrate on available algorithms and tools for calculating RNA secondary structures as the basis for further prediction or experimental determination of higher order structures. We give an introduction to the thermodynamic RNA folding model and an overview of methods to predict thermodynamically optimal and suboptimal secondary structures (with and without pseudoknots) for a single RNA. Furthermore, we summarize methods that predict a common or consensus structure for a set of homologous RNAs; such methods take advantage of the fact that the structures of noncoding RNAs are more conserved and more critical for their biological function than their sequences.