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Structural insights into RNA processing by the human RISC-loading complex
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Document Title
Structural insights into RNA processing by the human RISC-loading complex
Author
Wang HW, Noland C, Siridechadilok B, Taylor DW, Ma EB, Felderer K, Doudna JA, Nogales E
Name from Authors Collection
Affiliations
University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; Yale University; National Science & Technology Development Agency - Thailand; National Center Genetic Engineering & Biotechnology (BIOTEC); Howard Hughes Medical Institute; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; University of California System; University of California Berkeley
Type
Article
Source Title
NATURE STRUCTURAL & MOLECULAR BIOLOGY
Year
2009
Volume
16
Issue
11
Page
1148-U4
Open Access
Green Accepted, Green Submitted
Publisher
NATURE PUBLISHING GROUP
DOI
10.1038/nsmb.1673
Format
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.
Funding Sponsor
US National Institutes of Health; Human Frontier Science Program; NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM073794] Funding Source: NIH RePORTER
License
Copyright
Rights
Springer Nature America, Inc.
Publication Source
WOS