Dicer functions in RNA interference and in synthesis of small RNA involved in developmental timing in C. elegans

  1. René F. Ketting1,4,
  2. Sylvia E.J. Fischer1,4,
  3. Emily Bernstein2,3,
  4. Titia Sijen1,
  5. Gregory J. Hannon3,5, and
  6. Ronald H.A. Plasterk1,5
  1. 1The Hubrecht Laboratory and Center for Biomedical Genetics, Uppsalalaan 8, Utrecht, The Netherlands; 2Graduate Program in Genetics, State University of New York at Stony Brook, Stony Brook, New York 11794, USA; 3Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA

Abstract

Double-stranded RNAs can suppress expression of homologous genes through an evolutionarily conserved process named RNA interference (RNAi) or post-transcriptional gene silencing (PTGS). One mechanism underlying silencing is degradation of target mRNAs by an RNP complex, which contains ∼22 nt of siRNAs as guides to substrate selection. A bidentate nuclease called Dicer has been implicated as the protein responsible for siRNA production. Here we characterize theCaenorhabditis elegans ortholog of Dicer (K12H4.8;dcr-1) in vivo and in vitro. dcr-1 mutants show a defect in RNAi. Furthermore, a combination of phenotypic abnormalities and RNA analysis suggests a role for dcr-1 in a regulatory pathway comprised of small temporal RNA (let-7) and its target (e.g., lin-41).

Keywords

Footnotes

  • 4 These authors contributed equally to this work.

  • 5 Corresponding authors.

  • E-MAIL hannon{at}cshl.org; FAX (516) 367-8874.

  • E-MAIL plasterk{at}niob.knaw.nl; FAX 31-302516464.

  • Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.927801.

    • Received July 12, 2001.
    • Accepted September 5, 2001.
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