Structure of Dicer and Mechanistic Implications for RNAi
- I.J. MacRAE*,‡,
- F. LI*,
- K. ZHOU*,‡,
- W.Z. CANDE*, and
- J.A. DOUDNA*,†,‡,§
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
- Copyright 2006, Cold Spring Harbor Laboratory Press