DDX6 is a positive regulator of Ataxin-2/PAPD4 cytoplasmic polyadenylation machinery
| Autor: | Shin-ichi Hoshino, Hiroto Inagaki, Nao Hosoda |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cytoplasm Polyadenylation RNA Stability Biophysics Regulator Biochemistry DEAD-box RNA Helicases 03 medical and health sciences 0302 clinical medicine PABPC1 Downregulation and upregulation Tandem Mass Spectrometry Proto-Oncogene Proteins Humans Protein Interaction Maps RNA Messenger Molecular Biology Ataxin-2 mRNA Cleavage and Polyadenylation Factors Messenger RNA Chemistry Polynucleotide Adenylyltransferase Translation (biology) Cell Biology RNA Helicase A Cell biology HEK293 Cells 030104 developmental biology 030220 oncology & carcinogenesis Ataxin Poly A Chromatography Liquid Protein Binding |
| Zdroj: | Biochemical and Biophysical Research Communications. 553:9-16 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2021.03.066 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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