Poly(A)-binding proteins are required for microRNA-mediated silencing and to promote target deadenylation in C.

Mathieu N Flamand1, Edlyn Wu2, Ajay Vashisht3

  • 1Department of Biochemistry, McGill University, Montreal, QC H3A 1A3, Canada Goodman Cancer Research Center, McGill University, Montreal, QC H3A 1A3, Canada.

Nucleic Acids Research
|April 21, 2016
PubMed

Insights

Cytoplasmic poly(A)-binding proteins (PABPs) are crucial for microRNA (miRNA)-mediated gene silencing in C. elegans. These proteins accelerate mRNA deadenylation and enable silencing through poly(A)-dependent and -independent mechanisms.

Area of Science:

  • Molecular Biology
  • Gene Regulation
  • RNA Biology

Background:

  • Cytoplasmic poly(A)-binding proteins (PABPs) are known to interact with mRNA 3' termini and translation initiation factors.
  • PABPs have been implicated in microRNA (miRNA)-mediated silencing in various model organisms, but through distinct mechanisms.
  • The specific roles and mechanisms of PABPs in miRNA-mediated silencing in Caenorhabditis elegans remain to be fully elucidated.

Purpose of the Study:

  • To investigate the involvement of C. elegans PABPs (PAB-1 and PAB-2) in miRNA-mediated gene silencing.
  • To elucidate the mechanisms by which PABPs contribute to miRNA silencing in C. elegans.
  • To refine the understanding of PABP functions in the context of translational control and mRNA decay pathways.

Main Methods:

  • Utilized a combination of genetic analyses in C. elegans.
  • Performed protein interaction studies to identify interacting partners.
  • Employed cell-free assays to dissect the biochemical mechanisms of PABP action.

Main Results:

  • C. elegans PABPs (PAB-1 and PAB-2) are essential for miRNA-mediated silencing during embryonic and larval development.
  • Depletion of PABPs leads to the loss of both poly(A)-dependent and -independent translational silencing.
  • PABPs accelerate miRNA-mediated deadenylation, with this process being influenced by 3'UTR sequences and the distance to the poly(A) tail.

Conclusions:

  • C. elegans PABPs play a multifaceted role in miRNA-mediated silencing.
  • PABPs facilitate miRNA-mediated silencing by promoting deadenylation and enabling miRNA-binding sites.
  • A model is proposed where PABPs loop the 3'UTR poly(A) tail to the miRISC and deadenylase complex.

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