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

Author

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  • Yueshuang Ke

    (The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University
    Institute of Genetics and Cytology, Northeast Normal University)

  • Yanlong Han

    (Institute of Genetics and Cytology, Northeast Normal University)

  • Xiaolan Guo

    (Institute of Genetics and Cytology, Northeast Normal University)

  • Jitao Wen

    (Institute of Genetics and Cytology, Northeast Normal University)

  • Ke Wang

    (Institute of Genetics and Cytology, Northeast Normal University)

  • Xue Jiang

    (Institute of Genetics and Cytology, Northeast Normal University)

  • Xue Tian

    (Institute of Genetics and Cytology, Northeast Normal University)

  • Xueqing Ba

    (The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University
    Institute of Genetics and Cytology, Northeast Normal University)

  • Istvan Boldogh

    (Sealy Center for Molecular Medicine, University of Texas Medical Branch at Galveston)

  • Xianlu Zeng

    (The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University
    Institute of Genetics and Cytology, Northeast Normal University)

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.

Suggested Citation

  • Yueshuang Ke & Yanlong Han & Xiaolan Guo & Jitao Wen & Ke Wang & Xue Jiang & Xue Tian & Xueqing Ba & Istvan Boldogh & Xianlu Zeng, 2017. "PARP1 promotes gene expression at the post-transcriptional level by modulating the RNA-binding protein HuR," Nature Communications, Nature, vol. 8(1), pages 1-16, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14632
    DOI: 10.1038/ncomms14632
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