1. MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK
2. Present address: Department of Biochemistry and Molecular Biophysics, Columbia University, 701 West 168th Street, New York, New York 10032, USA.

Correspondence to: Kiyoshi Nagai² Correspondence and requests for materials should be addressed to K.N. (e-mail: Email: kn@mrc-lmb.cam.ac.uk).The coordinates have been deposited in the Prote in Data bank, accession code 1A9N.

Abstract

We have determined the crystal structure at 2.4 å resolution of a ternary complex between the spliceosomal U2B"/U2A' protein complex and hairpin-loop IV of U2 small nuclear RNA. Unlike its close homologue the U1A protein, U2B" binds to its cognate RNA only in the presence of U2A', which contains leucine-rich repeats in its sequence. The concave surface of a parallel -sheet within the leucine-rich-repeat region of U2A' interacts with the ribonucleoprotein domain of U2B" on the surface opposite its RNA-binding surface. The basic carboxy-terminal region of U2A' interacts with the RNA stem. The crystal structure reveals how protein–protein interaction regulates RNA-binding specificity, and how replacing only a few key residues allows the U2B" and U1A proteins to discriminate between their cognate RNA hairpins by forming alternative networks of interactions.