The C. elegans microRNA let-7 binds to imperfect let-7 complementary sites from the lin-41 3′UTR

  1. Monica C. Vella1,
  2. Eun-Young Choi1,2,
  3. Shin-Yi Lin1,3,
  4. Kristy Reinert1, and
  5. Frank J. Slack1,4
  1. 1Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, Connecticut 06520, USA

Abstract

Caenorhabditis elegans let-7, a founding member of the microRNA family, is predicted to bind to six sites in the 3′UTR of the mRNA of its target gene, lin-41, to down-regulate LIN-41. Here, we demonstrate that wild-type let-7 microRNA binds in vitro to RNA from the lin-41 3′UTR. This interaction is dependent on two conserved let-7 complementary sites (LCSs). A 27-nucleotide sequence between the LCSs is also necessary for down-regulation in vivo. LCS mutations compensatory to the lesion in let-7(n2853) can partially restore lin-41 3′UTR function in a let-7(n2853) background, providing the first experimental evidence for an animal miRNA binding directly to its validated target in vivo.

Keywords

Footnotes

  • Supplemental material is available at http://www.genesdev.org.

  • Article published online ahead of print. Article and publication date are at http://www.genesdev.org/cgi/doi/10.1101/gad.1165404.

  • 2 Present address: Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA

  • 3 Present address: Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.

  • 4 Corresponding author. E-MAIL frank.slack{at}yale.edu; FAX (203) 432-6161.

    • Accepted December 8, 2003.
    • Received October 28, 2003.
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