Structural Insight Into the Mechanism of Double-Stranded RNA Processing by Ribonuclease III

Cell. 2006 Jan 27;124(2):355-66. doi: 10.1016/j.cell.2005.11.034.

Abstract

Members of the ribonuclease III (RNase III) family are double-stranded RNA (dsRNA) specific endoribonucleases characterized by a signature motif in their active centers and a two-base 3' overhang in their products. While Dicer, which produces small interfering RNAs, is currently the focus of intense interest, the structurally simpler bacterial RNase III serves as a paradigm for the entire family. Here, we present the crystal structure of an RNase III-product complex, the first catalytic complex observed for the family. A 7 residue linker within the protein facilitates induced fit in protein-RNA recognition. A pattern of protein-RNA interactions, defined by four RNA binding motifs in RNase III and three protein-interacting boxes in dsRNA, is responsible for substrate specificity, while conserved amino acid residues and divalent cations are responsible for scissile-bond cleavage. The structure reveals a wealth of information about the mechanism of RNA hydrolysis that can be extrapolated to other RNase III family members.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Catalysis
  • Conserved Sequence
  • Crystallography, X-Ray
  • Dimerization
  • Macromolecular Substances / chemistry
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Binding
  • Protein Structure, Tertiary
  • RNA Interference
  • RNA, Double-Stranded / chemistry*
  • RNA, Double-Stranded / metabolism*
  • Ribonuclease III / chemistry*
  • Ribonuclease III / physiology*
  • Sequence Alignment
  • Substrate Specificity

Substances

  • Macromolecular Substances
  • RNA, Double-Stranded
  • Ribonuclease III