MicroRNA silencing through RISC recruitment of eIF6

Nature. 2007 Jun 14;447(7146):823-8. doi: 10.1038/nature05841. Epub 2007 May 16.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / growth & development
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Line
  • Eukaryotic Initiation Factors / metabolism*
  • Gene Silencing*
  • Humans
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism*
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / metabolism
  • Nuclear Proteins / genetics
  • RNA Interference
  • RNA, Helminth / genetics
  • RNA, Helminth / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA-Binding Proteins / metabolism
  • RNA-Induced Silencing Complex / metabolism*
  • Repressor Proteins / genetics

Substances

  • Caenorhabditis elegans Proteins
  • EIF6 protein, human
  • Eukaryotic Initiation Factors
  • LIN-14 protein, C elegans
  • LIN-28 protein, C elegans
  • MicroRNAs
  • Multiprotein Complexes
  • Nuclear Proteins
  • RNA, Helminth
  • RNA, Messenger
  • RNA-Binding Proteins
  • RNA-Induced Silencing Complex
  • Repressor Proteins
  • eif-6 protein, C elegans
  • lin-4 microRNA, C elegans
  • mirnlet7 microRNA, human
  • trans-activation responsive RNA-binding protein