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DDX6 is a positive regulator of Ataxin-2/PAPD4 cytoplasmic polyadenylation machinery

Hiroto Inagaki1, Nao Hosoda1, Shin-Ichi Hoshino1

  • 1Department of Biological Chemistry, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, 467-8603, Japan.

Biochemical and Biophysical Research Communications
|March 23, 2021
PubMed

Insights

The DEAD-box RNA helicase DDX6 positively regulates cytoplasmic polyadenylation mediated by the RNA-binding protein Ataxin-2. This interaction is crucial for maintaining the poly(A) tail length of Ataxin-2 target mRNAs and their subsequent protein expression.

Area of Science:

  • Molecular Biology
  • RNA Biology
  • Gene Regulation

Background:

  • Ataxin-2 is an RNA-binding protein that controls mRNA translation and stability.
  • Cytoplasmic polyadenylation is a key mechanism for regulating gene expression post-transcriptionally.

Purpose of the Study:

  • To identify novel regulators of Ataxin-2-mediated cytoplasmic polyadenylation.
  • To elucidate the role of DDX6 in Ataxin-2-dependent mRNA processing.

Main Methods:

  • Proteomic analysis (LC-MS/MS) to identify Ataxin-2 interacting partners.
  • RNA interference (RNAi) to downregulate DDX6 and Ataxin-2.
  • Poly(A) tail length analysis of target mRNAs.
  • Western blotting to assess protein expression.

Main Results:

  • DDX6 was identified as a novel positive regulator interacting with Ataxin-2 and its associated polyadenylation factors (PABPC1, PAPD4).
  • Downregulation of DDX6 phenocopied Ataxin-2 downregulation, increasing short poly(A) tails and decreasing protein levels of target mRNAs.
  • DDX6 is essential for Ataxin-2-induced polyadenylation, as DDX6 knockdown impaired Ataxin-2 overexpression effects, but not Ataxin-2 tethering-induced polyadenylation.

Conclusions:

  • DDX6 positively regulates Ataxin-2-induced cytoplasmic polyadenylation.
  • DDX6 likely facilitates Ataxin-2 binding to target mRNAs, thereby maintaining poly(A) tail length and promoting protein expression.
Keywords:
Ataxin-2Cytoplasmic polyadenylationDDX6Polyglutamine disease

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