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MicroRNA silencing through RISC recruitment of eIF6

Author

Listed:
  • Thimmaiah P. Chendrimada

    (The Wistar Institute, 3601 Spruce Street, and)

  • Kenneth J. Finn

    (University of California, San Diego, La Jolla, California 92093-0349, USA)

  • Xinjun Ji

    (University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA)

  • David Baillat

    (The Wistar Institute, 3601 Spruce Street, and
    Present address: Center de Regulacio Genomica Dr. Aiguader, 88 08003 Barcelona, Spain.)

  • Richard I. Gregory

    (The Wistar Institute, 3601 Spruce Street, and)

  • Stephen A. Liebhaber

    (University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA)

  • Amy E. Pasquinelli

    (University of California, San Diego, La Jolla, California 92093-0349, USA)

  • Ramin Shiekhattar

    (The Wistar Institute, 3601 Spruce Street, and
    Present address: Center de Regulacio Genomica Dr. Aiguader, 88 08003 Barcelona, Spain.)

Abstract

MicroRNAs (miRNAs) are a class of small RNAs that act post-transcriptionally to regulate messenger RNA stability and translation. To elucidate how miRNAs mediate their repressive effects, we performed biochemical and functional assays to identify new factors in the miRNA pathway. Here we show that human RISC (RNA-induced silencing complex) associates with a multiprotein complex containing MOV10—which is the homologue of Drosophila translational repressor Armitage—and proteins of the 60S ribosome subunit. Notably, this complex contains the anti-association factor eIF6 (also called ITGB4BP or p27BBP), a ribosome inhibitory protein known to prevent productive assembly of the 80S ribosome. Depletion of eIF6 in human cells specifically abrogates miRNA-mediated regulation of target protein and mRNA levels. Similarly, depletion of eIF6 in Caenorhabditis elegans diminishes lin-4 miRNA-mediated repression of the endogenous LIN-14 and LIN-28 target protein and mRNA levels. These results uncover an evolutionarily conserved function of the ribosome anti-association factor eIF6 in miRNA-mediated post-transcriptional silencing.

Suggested Citation

  • Thimmaiah P. Chendrimada & Kenneth J. Finn & Xinjun Ji & David Baillat & Richard I. Gregory & Stephen A. Liebhaber & Amy E. Pasquinelli & Ramin Shiekhattar, 2007. "MicroRNA silencing through RISC recruitment of eIF6," Nature, Nature, vol. 447(7146), pages 823-828, June.
    • Handle: RePEc:nat:nature:v:447:y:2007:i:7146:d:10.1038_nature05841
    DOI: 10.1038/nature05841
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