siRNAs can function as miRNAs

  1. John G. Doench1,3,
  2. Christian P. Petersen1,3, and
  3. Phillip A. Sharp1,2,4
  1. 1Center for Cancer Research, Department of Biology, and 2McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA

Abstract

With the discovery of RNA interference (RNAi) and related phenomena, new regulatory roles attributed to RNA continue to emerge. Here we show, in mammalian tissue culture, that a short interfering RNA (siRNA) can repress expression of a target mRNA with partially complementary binding sites in its 3′ UTR, much like the demonstrated function of endogenously encoded microRNAs (miRNAs). The mechanism for this repression is cooperative, distinct from the catalytic mechanism of mRNA cleavage by siRNAs. The use of siRNAs to study translational repression holds promise for dissecting the sequence and structural determinants and general mechanism of gene repression by miRNAs.

Keywords

Footnotes

  • 3 These authors contributed equally.

  • 4 Corresponding author.

  • E-MAIL sharppa{at}mit.edu; FAX (617) 253-3867.

  • Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.1064703.

    • Received December 6, 2002.
    • Accepted January 8, 2003.
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