title: PARP1 promotes gene expression at the post-transcriptiona level by modulating the RNA-binding protein HuR.
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.
authors.affiliation: The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun, Jilin 130024, China.|Institute of Genetics and Cytology, Northeast Normal University, Changchun, Jilin 130024, China.
authors.forename: Yueshuang
authors.initials: Y
authors.lastname: Ke
authors.affiliation: Institute of Genetics and Cytology, Northeast Normal University, Changchun, Jilin 130024, China.
authors.forename: Yanlong
authors.initials: Y
authors.lastname: Han
authors.affiliation: Institute of Genetics and Cytology, Northeast Normal University, Changchun, Jilin 130024, China.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Guo
authors.affiliation: Institute of Genetics and Cytology, Northeast Normal University, Changchun, Jilin 130024, China.
authors.forename: Jitao
authors.initials: J
authors.lastname: Wen
authors.affiliation: Institute of Genetics and Cytology, Northeast Normal University, Changchun, Jilin 130024, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Wang
authors.affiliation: Institute of Genetics and Cytology, Northeast Normal University, Changchun, Jilin 130024, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Institute of Genetics and Cytology, Northeast Normal University, Changchun, Jilin 130024, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Tian
authors.affiliation: The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun, Jilin 130024, China.|Institute of Genetics and Cytology, Northeast Normal University, Changchun, Jilin 130024, China.
authors.forename: Xueqing
authors.initials: X
authors.lastname: Ba
authors.affiliation: Department of Microbiology and Immunology, Sealy Center for Molecular Medicine, University of Texas Medical Branch at Galveston, Galveston, Texas 77555, USA.
authors.forename: Istvan
authors.initials: I
authors.lastname: Boldogh
authors.affiliation: The Key Laboratory of Molecular Epigenetics of the Ministry of Education, Northeast Normal University, Changchun, Jilin 130024, China.|Institute of Genetics and Cytology, Northeast Normal University, Changchun, Jilin 130024, China.
authors.forename: Xianlu
authors.initials: X
authors.lastname: Zeng
mesh_terms: D000818:Animals; D018925:Chemokines / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D000067780:ELAV-Like Protein 1 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D009154:Mutation; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology; D000074747:Poly ADP Ribosylation; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000494:pharmacology; D011499:Protein Processing, Post-Translational / Q000235:genetics*; D021381:Protein Transport; D000067996:RAW 264.7 Cells; D012333:RNA, Messenger / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018925:Chemokines; D016207:Cytokines; D000067780:ELAV-Like Protein 1; C000593997:Elavl1 protein, mouse; D008070:Lipopolysaccharides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D012333:RNA, Messenger; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1