A systematic survey of PRMT interactomes reveals the key roles of arginine methylation in the global control of RNA splicing and translation  

PRMT互作组的系统性研究揭示了精氨酸甲基化在剪接和翻译中的关键功能

作　　者：Huan-Huan Wei Xiao-Juan Fan Yue Hu Xiao-Xu Tian Meng Guo Miao-Wei Mao Zhao-Yuan Fang Ping Wu Shuai-Xin Gao Chao Peng Yun Yang Zefeng Wang 魏欢欢;樊晓娟;胡玥;田晓旭;郭萌;茅繆伟;方兆元;吴萍;高帅鑫;彭超;杨赟;王泽峰(CAS Key Laboratory of Computational Biology,Bio-Med Big Data Center,Shanghai Institute of Nutrition and Health,CAS Center for Excellence in Molecular Cell Science,University of Chinese Academy of Sciences,Chinese Academy of Sciences,Shanghai 200031,China;National Facility for Protein Science in Shanghai,Zhang-Jiang Lab,Shanghai Advanced Research Institute,Chinese Academy of Sciences,Shanghai 201210,China;Xijing Hospital of Digestive Diseases,Fourth Military Medical University,Xi’an 710000,China)

机构地区：[1]CAS Key Laboratory of Computational Biology,Bio-Med Big Data Center,Shanghai Institute of Nutrition and Health,CAS Center for Excellence in Molecular Cell Science,University of Chinese Academy of Sciences,Chinese Academy of Sciences,Shanghai 200031,China [2]National Facility for Protein Science in Shanghai,Zhang-Jiang Lab,Shanghai Advanced Research Institute,Chinese Academy of Sciences,Shanghai 201210,China [3]Xijing Hospital of Digestive Diseases,Fourth Military Medical University,Xi’an 710000,China

出　　处：《Science Bulletin》2021年第13期1342-1357,M0004,共17页科学通报（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(31730110,31661143031,91940303,and 91753135);the Science and Technology Commission of Shanghai Municipality grant(17JC1404900,18XD1404400,and 20ZR1467300);a Joint Research grant with State Key Laboratory of Microbial Metabolism,School of Life Science and Biotechnology,Shanghai Jiao Tong University(MMLKF16-11).

摘　　要：Thousands of proteins undergo arginine methylation,a widespread post-translational modification catalyzed by several protein arginine methyltransferases(PRMTs).However,global understanding of their biological functions is limited due to the lack of a complete picture of the catalytic network for each PRMT.Here,we systematically identified interacting proteins for all human PRMTs and demonstrated their functional importance in mRNA splicing and translation.We demonstrated significant overlapping of interactomes of human PRMTs with the known methylarginine-containing proteins.Different PRMTs are functionally redundant with a high degree of overlap in their substrates and high similarities between their putative methylation motifs.Importantly,RNA-binding proteins involved in regulating RNA splicing and translation contain highly enriched arginine methylation regions.Moreover,inhibition of PRMTs globally alternates alternative splicing(AS)and suppresses translation.In particular,ribosomal proteins are extensively modified with methylarginine,and mutations in their methylation sites suppress ribosome assembly,translation,and eventually cell growth.Collectively,our study provides a global view of different PRMT networks and uncovers critical functions of arginine methylation in regulating mRNA splicing and translation.目前对每种精氨酸甲基转移酶(PRMT)的催化网络缺乏完整了解,并且因为缺乏可靠的抗体和定义明确的“擦除器”和“读取器”,限制了其分子机制和生物学功能研究.本研究应用蛋白质组学技术系统性鉴定了人类细胞中已知的所有9个PRMT的蛋白互作组,并利用多种测序技术(包括RNA测序和核糖体印迹测序等),结合生物信息学分析,系统性地将每个PRMT和其精氨酸甲基化事件联系起来,并提供了PRMT生物学功能的新见解,揭示了精氨酸甲基化在调节RNA剪接和翻译中的重要功能.

关 键 词：Post-translational modification Protein arginine methyltransferase RNA-binding protein Ribosomal proteins Alternative splicing mRNA translation 

分 类 号：Q75[生物学—分子生物学]