Structure of Dicer and Mechanistic Implications for RNAi

  1. I.J. MacRAE*,,
  2. F. LI*,
  3. K. ZHOU*,,
  4. W.Z. CANDE*, and
  5. J.A. DOUDNA*,,,§
  1. *Department of Molecular and Cell Biology,
  2. Department of Chemistry,
  3. Howard Hughes Medical Institute, University of California, Berkeley, California 94720;
  4. §Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720

Abstract

Dicer is a specialized ribonuclease that processes double-stranded RNA (dsRNA) into small RNA fragments about25 nucleotides in length during the initiation phase of RNA interference (RNAi). We previously determined the crystalstructure of a Dicer enzyme from the diplomonad Giardia intestinalis and proposed a structural model for dsRNA processing.Here, we provide evidence that Dicer is composed of three structurally rigid regions connected by flexible hinges andpropose that conformational flexibility facilitates dsRNA binding and processing. We also examine the role of the accessorydomains found in Dicers of higher eukaryotes but absent in Giardia Dicer. Finally, we combine the structure ofDicer with published biochemical data to propose a model for the architecture of the RNA-induced silencing complex(RISC)-loading complex.

Footnotes

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