Structural basis for double-stranded RNA processing by Dicer

Science. 2006 Jan 13;311(5758):195-8. doi: 10.1126/science.1121638.

Abstract

The specialized ribonuclease Dicer initiates RNA interference by cleaving double-stranded RNA (dsRNA) substrates into small fragments about 25 nucleotides in length. In the crystal structure of an intact Dicer enzyme, the PAZ domain, a module that binds the end of dsRNA, is separated from the two catalytic ribonuclease III (RNase III) domains by a flat, positively charged surface. The 65 angstrom distance between the PAZ and RNase III domains matches the length spanned by 25 base pairs of RNA. Thus, Dicer itself is a molecular ruler that recognizes dsRNA and cleaves a specified distance from the helical end.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Conserved Sequence
  • Crystallography, X-Ray
  • Giardia lamblia / enzymology
  • Humans
  • Lanthanoid Series Elements / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • RNA Interference
  • RNA, Double-Stranded / metabolism*
  • RNA, Protozoan / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Ribonuclease III / chemistry*
  • Ribonuclease III / metabolism
  • Schizosaccharomyces / genetics
  • Structure-Activity Relationship

Substances

  • Lanthanoid Series Elements
  • RNA, Double-Stranded
  • RNA, Protozoan
  • Recombinant Fusion Proteins
  • Dicer protein, Giardia intestinalis
  • Ribonuclease III

Associated data

  • PDB/2FFL