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 2.4 Angstrom 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 p-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 U1B proteins to discriminate between their cognate RNA hairpins by forming alternative networks of interactions.