The RNA-binding protein Ataxin-2 regulates translation and mRNA stability through cytoplasmic polyadenylation of the targets. Here we newly identified DDX6 as a positive regulator of the cytoplasmic polyadenylation. Analysis of Ataxin-2 interactome using LC-MS/MS revealed prominent interaction with the DEAD-box RNA helicase DDX6. DDX6 interacted with components of the Ataxin-2 polyadenylation machinery; Ataxin-2, PABPC1 and PAPD4. As in the case for Ataxin-2 downregulation, DDX6 downregulation led to an increase in Ataxin-2 target mRNAs with short poly(A) tails as well as a reduction in their protein expression. In contrast, Ataxin-2 target mRNAs with short poly(A) tails were decreased by the overexpression of Ataxin-2, which was compromised by the DDX6 downregulation. However, polyadenylation induced by Ataxin-2 tethering was not affected by the DDX6 downregulation. Taken together, these results suggest that DDX6 positively regulates Ataxin-2-induced cytoplasmic polyadenylation to maintain poly(A) tail length of the Ataxin-2 targets provably through accelerating binding of Ataxin-2 to the target mRNAs.
Keywords: Ataxin-2; Cytoplasmic polyadenylation; DDX6; Polyglutamine disease.
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