The C-terminal domains of human TNRC6A, TNRC6B, and TNRC6C silence bound transcripts independently of Argonaute proteins

  1. Daniela Lazzaretti1,
  2. Isabelle Tournier1 and
  3. Elisa Izaurralde
  1. Max Planck Institute for Developmental Biology, D-72076 Tübingen, Germany
    1. 1 These authors contributed equally to this work.

    Abstract

    Proteins of the GW182 family are essential components of the miRNA pathway in animal cells. Vertebrate genomes encode three GW182 paralogs (TNRC6A, TNRC6B, and TNRC6C), which may be functionally redundant. Here, we show that the N-terminal GW-repeat-containing regions of all three TNRC6s interact with the four human Argonaute proteins (AGO1–AGO4). We also show that TNRC6A, TNRC6B, and TNRC6C silence the expression of bound mRNAs. This activity is mediated by their C-terminal silencing domains, and thus, is independent of the interaction with AGO1–AGO4. Silencing by TNRC6A, TNRC6B, and TNRC6C is effected by changes in protein expression and mRNA stability that can, in part, be attributed to deadenylation. Our findings indicate that TNRC6A, TNRC6B, and TNRC6C are recruited to miRNA targets through an interaction between their N-terminal domain and an Argonaute protein; the TNRC6s then promote translational repression and/or degradation of miRNA targets through a C-terminal silencing domain.

    Keywords

    Footnotes

    • Reprint requests to: Elisa Izaurralde, Max Planck Institute for Developmental Biology, Spemannstrasse 35, D-72076 Tübingen, Germany; e-mail: elisa.izaurralde{at}tuebingen.mpg.de; fax: +49-7071-601-1353.

    • Article published online ahead of print. Article and publication date are at http://www.rnajournal.org/cgi/doi/10.1261/rna.1606309.

      • Received February 17, 2009.
      • Accepted March 17, 2009.
    • Freely available online through the open access option.

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