Crystal structure of the spliceosomal U2B''-U2A' protein complex bound to a fragment of U2 small nuclear RNA

We have determined the crystal structure at 2.4å 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 β-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.