17 RNA Recognition by Proteins

Abstract

Many RNA molecules are recognized by proteins that interact preferentially with a particular RNA molecule. We address here the structural principles by which these proteins recognize their target nucleic acid. RNA molecules invariably consist of duplex regions that are A-form, often stacked one on another, as well as regions of single-stranded loops and bulges giving rise in general to the possibility of a more complex and richly varied three-dimensional shape than can be assumed by duplex DNA. Although the structural database for RNA-binding proteins and their complexes with RNA is still smaller than for DNA-binding proteins, it has expanded rapidly in the past few years. As a consequence, some patterns of similarities and differences in the structural basis of recognition by proteins can be seen at this time.

Structural, biochemical, and molecular genetic studies of protein–RNA complexes have established at least four important sources of sequence specificity in protein–RNA interactions: (1) Direct hydrogen bonding and van der Waals interactions between protein side chains and the exposed edges of base pairs provide structural complementarity to the correct but not to the incorrect sequences. The interactions in the major groove can distinguish between all four Watson-Crick base pairs, whereas interactions in the minor groove can only distinguish between G-C and A-T. However, the formation of duplex RNA in loop regions from non-canonical base pairs presents a far more varied pattern of hydrogen-bond donors and acceptors in the minor groove which then forms an ideal target for protein recognition; (2) the...