GW182 proteins directly recruit cytoplasmic deadenylase complexes to miRNA targets

Joerg E Braun1, Eric Huntzinger, Maria Fauser

  • 1Department of Biochemistry, Max Planck Institute for Developmental Biology, Spemannstrasse 35, D-72076 Tübingen, Germany.

Molecular Cell
|October 11, 2011
PubMed

Insights

MicroRNAs (miRNAs) regulate gene expression by recruiting deadenylase complexes. GW182 proteins directly interact with these complexes, facilitating mRNA deadenylation and degradation, a key step in miRNA-mediated gene silencing.

Area of Science:

  • Molecular Biology
  • Gene Regulation
  • RNA Biology

Background:

  • MicroRNAs (miRNAs) are key posttranscriptional regulators of gene expression.
  • miRNA function involves association with Argonaute and GW182 proteins to repress translation and/or promote mRNA degradation.
  • miRNA-mediated mRNA degradation is initiated by deadenylation, but the mechanism of deadenylase recruitment remains unclear.

Purpose of the Study:

  • To investigate whether deadenylases are recruited directly to miRNA targets or as a consequence of translational repression.
  • To identify interactions between Argonaute/GW182 proteins and cytoplasmic deadenylase complexes.

Main Methods:

  • Screening for protein-protein interactions between Argonaute/GW182 proteins and subunits of cytoplasmic deadenylase complexes.
  • Investigating the functional significance of identified interactions in gene silencing.
  • Assessing the evolutionary conservation of these interactions.

Main Results:

  • Human GW182 proteins directly interact with the PAN2-PAN3 and CCR4-CAF1-NOT deadenylase complexes via PAN3 and NOT1, respectively.
  • These direct interactions are essential for miRNA-mediated gene silencing.
  • The identified interactions and their role in silencing are conserved in *Drosophila melanogaster*.

Conclusions:

  • GW182 proteins act as a scaffold, directly recruiting deadenylase complexes to the poly(A) tail of miRNA targets.
  • This recruitment facilitates direct deadenylation of miRNA targets.
  • Deadenylation is a direct consequence of miRNA regulation, not solely a result of translational blockade.

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