Specificity of ribonucleoprotein interaction determined by RNA folding during complex formation

Many proteins involved in pre-mRNA processing contain one or more copies of a 70-90-amino-acid alpha beta module called the ribonucleoprotein domain(1-4). RNA maturation depends on the specific recognition by ribonucleoproteins of RNA elements within pre-mRNAs and small nuclear RNAs. The human U1A protein binds an RNA hairpin during splicing(5-8), and regulates its own expression by binding an internal loop(9) in the 3'-untranslated region of its pre mRNA, preventing polyadenylation3. Here we report the nuclear magnetic resonance structure of the complex between the regulatory element of the U1A 3'-untranslated region (UTR)(9-11) and the U1A protein RNA-binding domain. Specific intermolecular recognition requires the interaction of the variable loops of the ribonucleoprotein domain with the well-structured helical regions of the RNA. Formation of the complex then orders the flexible RNA single-stranded loop against the protein beta-sheet surface, and reorganizes the carboxy-terminal region of the protein to maximize surface complementarity and functional group recognition.