Poly(ADP-ribosyl)ation enhances HuR oligomerization and contributes to pro-inflammatory gene mRNA stabilization
| Autor: | Xueqing Ba, Yueshuang Ke, Xianlu Zeng, Jing Zhang, Xingyue Fu, Xueping Lv, Istvan Boldogh, Wenjing Hao, Ruoxi Wang, Ameer Ali Bohio |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Untranslated region
Lipopolysaccharides DNA Repair DNA damage Neutrophils RNA Stability Poly (ADP-Ribose) Polymerase-1 PARP1 ELAV-Like Protein 1 03 medical and health sciences Cellular and Molecular Neuroscience Poly ADP Ribosylation 0302 clinical medicine Gene expression Gene silencing Oligomerization Animals Humans mRNA stability RNA Messenger Molecular Biology 030304 developmental biology Pharmacology Regulation of gene expression Inflammation 0303 health sciences Chemistry Translation (biology) Cell Biology MRNA stabilization Cell biology Disease Models Animal Gene Expression Regulation 030220 oncology & carcinogenesis Molecular Medicine HuR Original Article Protein Processing Post-Translational DNA Damage |
| Zdroj: | Cellular and Molecular Life Sciences |
| ISSN: | 1420-9071 1420-682X |
| Popis: | 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. Electronic supplementary material The online version of this article (10.1007/s00018-020-03618-4) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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