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PARP1 promotes gene expression at the post-transcriptiona level by modulating the RNA-binding protein HuR.
- Source :
-
Nature communications [Nat Commun] 2017 Mar 08; Vol. 8, pp. 14632. Date of Electronic Publication: 2017 Mar 08. - Publication Year :
- 2017
-
Abstract
- Poly(ADP-ribosyl)ation (PARylation) is mainly catalysed by poly-ADP-ribose polymerase 1 (PARP1), whose role in gene transcription modulation has been well established. Here we show that, in response to LPS exposure, PARP1 interacts with the adenylateuridylate-rich element-binding protein embryonic lethal abnormal vision-like 1 (Elavl1)/human antigen R (HuR), resulting in its PARylation, primarily at site D226. PARP inhibition and the D226 mutation impair HuR's PARylation, nucleocytoplasmic shuttling and mRNA binding. Increases in mRNA level or stability of pro-inflammatory cytokines/chemokines are abolished by PARP1 ablation or inhibition, or blocked in D226A HuR-expressing cells. The present study demonstrates a mechanism to regulate gene expression at the post-transcriptional level, and suggests that blocking the interaction of PARP1 with HuR could be a strategy to treat inflammation-related diseases that involve increased mRNA stability.
- Subjects :
- Animals
Chemokines immunology
Cytokines immunology
ELAV-Like Protein 1 immunology
ELAV-Like Protein 1 metabolism
HEK293 Cells
Humans
Inflammation immunology
Lipopolysaccharides pharmacology
Macrophages, Peritoneal drug effects
Mice
Mutation
Poly (ADP-Ribose) Polymerase-1 antagonists & inhibitors
Poly (ADP-Ribose) Polymerase-1 immunology
Poly ADP Ribosylation
Poly(ADP-ribose) Polymerase Inhibitors pharmacology
Protein Transport
RAW 264.7 Cells
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
ELAV-Like Protein 1 genetics
Gene Expression Regulation
Inflammation genetics
Macrophages, Peritoneal immunology
Poly (ADP-Ribose) Polymerase-1 genetics
Protein Processing, Post-Translational genetics
RNA, Messenger metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 8
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 28272405
- Full Text :
- https://doi.org/10.1038/ncomms14632