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Nat Struct Mol Biol. 2009 Nov;16(11):1148-53. doi: 10.1038/nsmb.1673. Epub 2009 Oct 11.

Structural insights into RNA processing by the human RISC-loading complex.

Author information

1
Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA. hongwei.wang@yale.edu

Abstract

Targeted gene silencing by RNA interference (RNAi) requires loading of a short guide RNA (small interfering RNA (siRNA) or microRNA (miRNA)) onto an Argonaute protein to form the functional center of an RNA-induced silencing complex (RISC). In humans, Argonaute2 (AGO2) assembles with the guide RNA-generating enzyme Dicer and the RNA-binding protein TRBP to form a RISC-loading complex (RLC), which is necessary for efficient transfer of nascent siRNAs and miRNAs from Dicer to AGO2. Here, using single-particle EM analysis, we show that human Dicer has an L-shaped structure. The RLC Dicer's N-terminal DExH/D domain, located in a short 'base branch', interacts with TRBP, whereas its C-terminal catalytic domains in the main body are proximal to AGO2. A model generated by docking the available atomic structures of Dicer and Argonaute homologs into the RLC reconstruction suggests a mechanism for siRNA transfer from Dicer to AGO2.

PMID:
19820710
PMCID:
PMC2845538
DOI:
10.1038/nsmb.1673
[Indexed for MEDLINE]
Free PMC Article

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