Probing RNA Structure and Function in Solution

Abstract

RNAs are unique among biological macromolecules because they can exhibit coding, information transfer, and catalysis activities. The biological functions of RNA are essentially encoded within its spatial folding, which potentiates the occurrence of stable or transient intra- or inter-molecular interactions. Thus, RNA function is intimately linked to its dynamic and versatile structure. Determination of RNA structure is one of the major goals in molecular biology. However, structure of RNA by itself is not necessarily of biological relevance, since RNA plays its biological role through interactions with ligands (RNA or proteins), and its structure can undergo conformational changes upon ligand binding. Therefore, the challenge of today’s molecular biology is to establish and understand the link between the structure and the function of RNA.

Because of its complex and versatile nature, RNA structure determination remains an arduous task. Although a number of RNA structures have been solved at high resolution by X-ray crystallography (see Holbrook, this volume), the major requirement for successful crystallization remains the stability of the studied molecule. In addition, the information is for the most part necessarily static. Techniques for nuclear magnetic resonance (NMR) analysis of RNA are improving rapidly, but so far rather small RNA molecules have been studied (for review, see Wyatt and Tinoco 1993). Besides these physical approaches, alternative and complementary strategies have been developed to study complex RNA structure in solution. These techniques include approaches for predicting (comparative sequence analysis, computer prediction, molecular modeling) and for testing experimentally the RNA structure (biochemical and genetic approaches).