Dicer is dispensable for asymmetric RISC loading in mammals

RNA. 2012 Jan;18(1):24-30. doi: 10.1261/rna.029785.111. Epub 2011 Nov 21.

Abstract

In flies, asymmetric loading of small RNA duplexes into Argonaute2-containing RNA-induced silencing complex (Ago2-RISC) requires Dicer-2/R2D2 heterodimer, which acts as a protein sensor for the thermodynamic stabilities of the ends of small RNA duplexes. However, the mechanism of small RNA asymmetry sensing in mammalian RISC assembly remains obscure. Here, we quantitatively examined RISC assembly and target silencing activity in the presence or absence of Dicer in mammals. Our data show that, unlike the well-characterized fly Ago2-RISC assembly pathway, mammalian Dicer is dispensable for asymmetric RISC loading in vivo and in vitro.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line
  • DEAD-box RNA Helicases / chemistry
  • DEAD-box RNA Helicases / genetics
  • DEAD-box RNA Helicases / metabolism*
  • Mice
  • RNA, Small Interfering / chemistry
  • RNA, Small Interfering / metabolism*
  • RNA-Induced Silencing Complex / chemistry
  • RNA-Induced Silencing Complex / genetics
  • RNA-Induced Silencing Complex / metabolism*
  • Ribonuclease III / chemistry
  • Ribonuclease III / genetics
  • Ribonuclease III / metabolism*

Substances

  • RNA, Small Interfering
  • RNA-Induced Silencing Complex
  • Dicer1 protein, mouse
  • Ribonuclease III
  • DEAD-box RNA Helicases