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GLS1-RNA Polymerase II Axis Mediates Glutamine-Dependent Hepatoprotective Effects on Alcoholic Liver Disease in High-Protein Diets

文献类型：期刊论文

作者Wu, Wenbiao7,8,9; Jiang, Haowen7,8; Liu, Yichang6; Peng, Chang7,8,9; Wang, Hanlin7; Yang, Wenhua5; Lyu, Zan4; Sun, Yan3; Ma, Huan7,8; Gu, Hongyu5
刊名ADVANCED SCIENCE
出版日期2025-09-11
页码16
关键词alcoholic fatty liver disease GLS1 hepatic lipogenesis high-protein diets RNA polymerase II
DOI10.1002/advs.202502738
通讯作者Jiang, Haowen(haowenjiang@simm.ac.cn) ; Wu, Rui(wurui@ucas.ac.cn) ; Li, Jinlong(jinlongli@ntu.edu.cn) ; Li, Jia(jli@simm.ac.cn)
英文摘要The RNA polymerase II (RNA pol II) complex is essential for gene transcription throughout life, and numerous cofactors have been identified as critical for diverse transcriptional processes. Herein, it is discovered that the RNA pol II complex is modulated by glutaminase 1 (GLS1), which affects lipid metabolism. In alcoholic fatty liver disease (AFLD), RNA pol II activation is observed, whereas RNA pol II inhibition reverse hepatic steatosis. Furthermore, high-protein diets are recognized for their adjuvant effect on patients with AFLD; glutamine is indispensable for its protective effects against hepatic steatosis, which is dependent on RNA pol II. Mechanistically, GLS1 acts as a chaperone that affects the RNA pol II complex in the nucleus by interacting with its subunits, ROLR2H and POLR2E. In vivo studies have shown that hepatic overexpression of GLS1 ameliorates alcohol-induced fatty liver, whereas deficiency worsens this condition. Moreover, the overexpression of POLR2E or POLR2H, but not the truncated variants, abolishes the protective effects of GLS1 against alcohol-induced fatty liver. Thus, the study clarifies GLS1 as a cofactor involved in assembling the RNA pol II complex, regulating hepatic steatosis, and provides foundational insights for future therapeutic approaches in AFLD.
WOS关键词HEPATIC STEATOSIS ; TRANSCRIPTION ; PATHOGENESIS ; GAMMA ; MICE
资助项目National Natural Science Foundation of China
WOS研究方向Chemistry ; Science & Technology - Other Topics ; Materials Science
语种英语
WOS记录号WOS:001568661400001
出版者WILEY
源URL[http://119.78.100.183/handle/2S10ELR8/321438]  
专题中国科学院上海药物研究所
通讯作者Jiang, Haowen; Wu, Rui; Li, Jinlong; Li, Jia
作者单位1.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Shandong, Peoples R China
2.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528400, Guangdong, Peoples R China
3.Lingang Lab, Shanghai 201203, Peoples R China
4.Fudan Univ, Coll Pharm, Shanghai 210023, Peoples R China
5.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
6.Nantong Univ, Sch Pharm, Nantong 226019, Peoples R China
7.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Chem Biol, Shanghai 201203, Peoples R China
8.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China
9.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Hangzhou 310000, Peoples R China
推荐引用方式
GB/T 7714		 Wu, Wenbiao,Jiang, Haowen,Liu, Yichang,et al. GLS1-RNA Polymerase II Axis Mediates Glutamine-Dependent Hepatoprotective Effects on Alcoholic Liver Disease in High-Protein Diets[J]. ADVANCED SCIENCE,2025:16.
APA Wu, Wenbiao.,Jiang, Haowen.,Liu, Yichang.,Peng, Chang.,Wang, Hanlin.,...&Li, Jia.(2025).GLS1-RNA Polymerase II Axis Mediates Glutamine-Dependent Hepatoprotective Effects on Alcoholic Liver Disease in High-Protein Diets.ADVANCED SCIENCE,16.
MLA Wu, Wenbiao,et al."GLS1-RNA Polymerase II Axis Mediates Glutamine-Dependent Hepatoprotective Effects on Alcoholic Liver Disease in High-Protein Diets".ADVANCED SCIENCE (2025):16.

入库方式： OAI收割

来源：上海药物研究所

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