Poly(ADP-ribosyl)ation enhances HuR oligomerization and contributes to pro-inflammatory gene mRNA stabilization

Yueshuang Ke, Xueping Lv, Xingyue Fu, Jing Zhang, Ameer Ali Bohio, Xianlu Zeng, Wenjing Hao, Ruoxi Wang, Istvan Boldogh, Xueqing Ba

    Research output: Contribution to journalArticlepeer-review

    2 Scopus citations

    Abstract

    Poly(ADP-ribosyl)ation (PARylation) is an important post-translational modification mainly catalyzed by poly-ADP-ribose polymerase 1 (PARP1). In addition to having important roles in DNA damage detection and repair, it functions in gene expression regulation, especially at the posttranscriptional level. Embryonic lethal abnormal vision-like 1/human antigen R (ELAVL/HuR), a canonical 3′ untranslated region AU-rich element-binding protein, is a crucial mRNA-stabilizing protein that protects target mRNAs from RNA-destabilizing protein- or microRNA-induced silencing complex (miRISC)-mediated degradation. Additionally, in some cases, HuR itself either promotes or suppresses translation. Here, we demonstrated that in response to inflammatory stimuli, the PARylation of HuR, mostly at the conserved D226 site, by PARP1 increased the formation of the HuR oligomer/multimer, and HuR oligomerization promoted the disassociation of miRISC and stabilized the pro-inflammatory gene mRNAs. The prevention of PARP1 activation or HuR oligomerization attenuated lipopolysaccharide-induced inflammatory gene expression and the airway recruitment of neutrophils in mouse lungs. The present study verified a novel mechanism of PARP1 and HuR PARylation in the RNA stability regulation, increasing our understanding of how PARP1 regulates gene expression.

    Original languageEnglish (US)
    Pages (from-to)1817-1835
    Number of pages19
    JournalCellular and Molecular Life Sciences
    Volume78
    Issue number4
    DOIs
    StatePublished - Feb 2021

    Keywords

    • HuR
    • Inflammation
    • Oligomerization
    • PARP1
    • mRNA stability

    ASJC Scopus subject areas

    • Molecular Medicine
    • Molecular Biology
    • Pharmacology
    • Cellular and Molecular Neuroscience
    • Cell Biology

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