PARP1 promotes gene expression at the post-transcriptiona level by modulating the RNA-binding protein HuR

Yueshuang Ke, Yanlong Han, Xiaolan Guo, Jitao Wen, Ke Wang, Xue Jiang, Xue Tian, Xueqing Ba, Istvan Boldogh, Xianlu Zeng

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish (US)
Article number14632
JournalNature Communications
Volume8
DOIs
StatePublished - Mar 8 2017

Fingerprint

ribose
adenosine diphosphate
RNA-Binding Proteins
Poly(ADP-ribose) Polymerases
gene expression
antigens
Gene expression
Adenosine Diphosphate
proteins
Gene Expression
Antigens
Messenger RNA
RNA Stability
Chemokines
Carrier Proteins
Transcription
Ablation
Cytokines
Inflammation
Mutation

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

PARP1 promotes gene expression at the post-transcriptiona level by modulating the RNA-binding protein HuR. / Ke, Yueshuang; Han, Yanlong; Guo, Xiaolan; Wen, Jitao; Wang, Ke; Jiang, Xue; Tian, Xue; Ba, Xueqing; Boldogh, Istvan; Zeng, Xianlu.

In: Nature Communications, Vol. 8, 14632, 08.03.2017.

Research output: Contribution to journalArticle

Ke, Yueshuang ; Han, Yanlong ; Guo, Xiaolan ; Wen, Jitao ; Wang, Ke ; Jiang, Xue ; Tian, Xue ; Ba, Xueqing ; Boldogh, Istvan ; Zeng, Xianlu. / PARP1 promotes gene expression at the post-transcriptiona level by modulating the RNA-binding protein HuR. In: Nature Communications. 2017 ; Vol. 8.
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AU - Wang, Ke

AU - Jiang, Xue

AU - Tian, Xue

AU - Ba, Xueqing

AU - Boldogh, Istvan

AU - Zeng, Xianlu

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