Distinct roles for Drosophila Dicer-1 and Dicer-2 in the siRNA/miRNA silencing pathways

Cell. 2004 Apr 2;117(1):69-81. doi: 10.1016/s0092-8674(04)00261-2.

Abstract

The RNase III enzyme Dicer processes RNA into siRNAs and miRNAs, which direct a RNA-induced silencing complex (RISC) to cleave mRNA or block its translation (RNAi). We have characterized mutations in the Drosophila dicer-1 and dicer-2 genes. Mutation in dicer-1 blocks processing of miRNA precursors, whereas dicer-2 mutants are defective for processing siRNA precursors. It has been recently found that Drosophila Dicer-1 and Dicer-2 are also components of siRNA-dependent RISC (siRISC). We find that Dicer-1 and Dicer-2 are required for siRNA-directed mRNA cleavage, though the RNase III activity of Dicer-2 is not required. Dicer-1 and Dicer-2 facilitate distinct steps in the assembly of siRISC. However, Dicer-1 but not Dicer-2 is essential for miRISC-directed translation repression. Thus, siRISCs and miRISCs are different with respect to Dicers in Drosophila.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics*
  • Eye Abnormalities / genetics*
  • Female
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Molecular Sequence Data
  • Mutation / genetics
  • Protein Biosynthesis / genetics
  • Protein Structure, Tertiary / physiology
  • RNA Helicases / genetics
  • RNA Helicases / metabolism*
  • RNA Interference / physiology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / genetics*
  • RNA, Small Interfering / metabolism
  • RNA-Induced Silencing Complex / genetics
  • RNA-Induced Silencing Complex / metabolism
  • Ribonuclease III / genetics
  • Ribonuclease III / metabolism*
  • Sequence Homology, Amino Acid

Substances

  • Drosophila Proteins
  • MicroRNAs
  • RNA, Messenger
  • RNA, Small Interfering
  • RNA-Induced Silencing Complex
  • DCR-2 protein, Drosophila
  • Ribonuclease III
  • RNA Helicases