DDX6 is a positive regulator of Ataxin-2/PAPD4 cytoplasmic polyadenylation machinery.
Ataxin-2
/ metabolism
Chromatography, Liquid
Cytoplasm
/ metabolism
DEAD-box RNA Helicases
/ metabolism
HEK293 Cells
Humans
Poly A
/ genetics
Polyadenylation
Polynucleotide Adenylyltransferase
/ metabolism
Protein Binding
Protein Interaction Maps
Proto-Oncogene Proteins
/ metabolism
RNA Stability
RNA, Messenger
/ genetics
Tandem Mass Spectrometry
mRNA Cleavage and Polyadenylation Factors
/ metabolism
Ataxin-2
Cytoplasmic polyadenylation
DDX6
Polyglutamine disease
Journal
Biochemical and biophysical research communications
ISSN: 1090-2104
Titre abrégé: Biochem Biophys Res Commun
Pays: United States
ID NLM: 0372516
Informations de publication
Date de publication:
14 05 2021
14 05 2021
Historique:
received:
12
03
2021
accepted:
12
03
2021
pubmed:
24
3
2021
medline:
7
7
2021
entrez:
23
3
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33756349
pii: S0006-291X(21)00456-3
doi: 10.1016/j.bbrc.2021.03.066
pii:
doi:
Substances chimiques
ATXN2 protein, human
0
Ataxin-2
0
Proto-Oncogene Proteins
0
RNA, Messenger
0
mRNA Cleavage and Polyadenylation Factors
0
Poly A
24937-83-5
Polynucleotide Adenylyltransferase
EC 2.7.7.19
TENT2 protein, human
EC 2.7.7.19
DDX6 protein, human
EC 3.6.1.-
DEAD-box RNA Helicases
EC 3.6.4.13
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
9-16Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no conflict of interest.