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Argonaute2 cleaves the anti-guide strand of siRNA during RISC activation

Cell. 2005 Nov 18;123(4):621-9. doi: 10.1016/j.cell.2005.10.020. Epub 2005 Nov 3.

Abstract

The mRNA-cleavage step of RNA interference is mediated by an endonuclease, Argonaute2 (Ago2), within the RNA-induced silencing complex (RISC). Ago2 uses one strand of the small interfering (si) RNA duplex as a guide to find messenger RNAs containing complementary sequences and cleaves the phosphodiester backbone at a specific site measured from the guide strand's 5' end. Here, we show that both strands of siRNA get loaded onto Ago2 protein in Drosophila S2 cell extracts. The anti-guide strand behaves as a RISC substrate and is cleaved by Ago2. This cleavage event is important for the removal of the anti-guide strand from Ago2 protein and activation of RISC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Argonaute Proteins
  • Base Sequence
  • Cell Line
  • Cell-Free System
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism
  • Glucose / metabolism
  • Hexokinase / metabolism
  • RNA Interference*
  • RNA, Double-Stranded / genetics
  • RNA, Double-Stranded / metabolism
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • RNA-Induced Silencing Complex / metabolism*
  • Ribonuclease III / metabolism

Substances

  • AGO2 protein, Drosophila
  • Argonaute Proteins
  • Drosophila Proteins
  • RNA, Double-Stranded
  • RNA, Small Interfering
  • RNA-Induced Silencing Complex
  • Adenosine Triphosphate
  • Hexokinase
  • Ribonuclease III
  • Glucose