GW182 proteins directly recruit cytoplasmic deadenylase complexes to miRNA targets

Mol Cell. 2011 Oct 7;44(1):120-33. doi: 10.1016/j.molcel.2011.09.007.


miRNAs are posttranscriptional regulators of gene expression that associate with Argonaute and GW182 proteins to repress translation and/or promote mRNA degradation. miRNA-mediated mRNA degradation is initiated by deadenylation, although it is not known whether deadenylases are recruited to the mRNA target directly or by default, as a consequence of a translational block. To answer this question, we performed a screen for potential interactions between the Argonaute and GW182 proteins and subunits of the two cytoplasmic deadenylase complexes. We found that human GW182 proteins recruit the PAN2-PAN3 and CCR4-CAF1-NOT deadenylase complexes through direct interactions with PAN3 and NOT1, respectively. These interactions are critical for silencing and are conserved in D. melanogaster. Our findings reveal that GW182 proteins provide a docking platform through which deadenylase complexes gain access to the poly(A) tail of miRNA targets to promote their deadenylation, and they further indicate that deadenylation is a direct effect of miRNA regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / metabolism
  • Cytoplasm / metabolism*
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster
  • Exoribonucleases / metabolism
  • Gene Silencing
  • Genetic Complementation Test
  • HeLa Cells
  • Humans
  • MicroRNAs / metabolism*
  • Poly A / metabolism
  • Protein Interaction Mapping
  • Protein Structure, Tertiary
  • RNA-Binding Proteins
  • Receptors, CCR4 / metabolism
  • Retinoblastoma-Binding Protein 4 / metabolism
  • Ribonucleases / metabolism
  • Transcription Factors / metabolism


  • CCR4 protein, human
  • CNOT1 protein, human
  • CNOT8 protein, human
  • Caf1-55 protein, Drosophila
  • Carrier Proteins
  • Drosophila Proteins
  • Gw protein, Drosophila
  • MicroRNAs
  • NOT1 protein, Drosophila
  • PAN3 protein, human
  • RNA-Binding Proteins
  • Receptors, CCR4
  • Retinoblastoma-Binding Protein 4
  • Transcription Factors
  • Poly A
  • CCR4 protein, Drosophila
  • Exoribonucleases
  • PAN2 protein, Drosophila
  • Ribonucleases
  • PAN2 protein, human