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

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.

journal_name

Nat Struct Mol Biol

authors

Wang HW,Noland C,Siridechadilok B,Taylor DW,Ma E,Felderer K,Doudna JA,Nogales E

doi

10.1038/nsmb.1673

subject

Has Abstract

pub_date

2009-11-01 00:00:00

pages

1148-53

issue

11

eissn

1545-9993

issn

1545-9985

pii

nsmb.1673

journal_volume

16

pub_type

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