Specificity of ribonucleoprotein interaction determined by RNA folding during complex formulation

Nature. 1996 Apr 18;380(6575):646-50. doi: 10.1038/380646a0.


Many proteins involved in pre-mRNA processing contain one or more copies of a 70-90-amino-acid alphabeta module called the ribonucleoprotein domain. 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, and regulates its own expression by binding an internal loop in the 3'-untranslated region of its pre-mRNA, preventing polyadenylation. Here we report the nuclear magnetic resonance structure of the complex between the regulatory element of the U1A 3'-untranslated region (UTR) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Humans
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Sequence Data
  • Nucleic Acid Conformation
  • Protein Binding
  • Protein Conformation
  • RNA / chemistry*
  • RNA / metabolism
  • RNA-Binding Proteins / chemistry*
  • RNA-Binding Proteins / metabolism
  • Ribonucleoprotein, U1 Small Nuclear / chemistry*
  • Ribonucleoprotein, U1 Small Nuclear / metabolism


  • RNA-Binding Proteins
  • Ribonucleoprotein, U1 Small Nuclear
  • U1A protein
  • RNA