文献类型：期刊文献

英文题名：Global profiling of arginine dimethylation in regulating protein phase separation by a steric effect-based chemical-enrichment method

作者：Wang, Qi[1,2];Li, Zhouxian[1,3];Zhang, Shenqing[4];Li, Yichen[4];Wang, Yan[1,2];Fang, Zheng[1,2];Ma, Yanni[1,2];Liu, Zhen[1,2];Zhang, Weibing[3];Li, Dan[4,5];Liu, Cong[2,6,7];Ye, Mingliang[1,2]

机构：[1]Chinese Acad Sci, Dalian Inst Chem Phys, Key Lab Separat Sci Analyt Chem, Natl Chromatog Ctr,Natl Chromatog R&A Ctr, Dalian 116023, Peoples R China;[2]Univ Chinese Acad Sci, Beijing 100049, Peoples R China;[3]East China Univ Sci & Technol, Shanghai Key Lab Funct Mat Chem, Dept Chem & Mol Engn, Shanghai 200237, Peoples R China;[4]Shanghai Jiao Tong Univ, Bio X Inst, Key Lab Genet Dev & Neuropsychiat Disorders, Minist Educ, Shanghai 200030, Peoples R China;[5]Shanghai Jiao Tong Univ, Zhangjiang Inst Adv Study, Shanghai 200240, Peoples R China;[6]Chinese Acad Sci, Shanghai Inst Organ Chem, Interdisciplinary Res Ctr Biol & Chem, Shanghai 201210, Peoples R China;[7]Univ Chinese Acad Sci, Shanghai Inst Organ Chem, State Key Lab Bio Organ & Nat Prod Chem, Shanghai 200032, Peoples R China

年份：2022

卷号：119

期号：43

外文期刊名：PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001016355600006)】；

基金：This work was supported, in part, by the National Key Research and Development Program of China (grants 2021YFA1302602, 2020YFE0202200, and 2019YFE0120600), the National Natural Science Foundation of China (grants 21974045, 91753105, 92153302, 82188101, 32170683, 31872716, and 32171236), the innovation program (DICP & QIBEBT UN201802) of science and research from the DICP, CAS, and Innovation Academy for Precision Measurement Science and Technology, CAS, the Science and Technology Commission of Shanghai Municipality (grants 20XD1425000 and 2019SHZDZX02), the Shanghai Pilot Program for Basic Research, Chinese Academy of Science, Shanghai Branch (grant CYJ-SHFY-2022-005).

语种：英文

外文关键词：arginine dimethylation; chemical-enrichment method; RG/RGG motif; liquid-liquid phase separation; stress granule

摘要：Protein arginine methylation plays an important role in regulating protein functions in different cellular processes, and its dysregulation may lead to a variety of human diseases. Recently, arginine methylation was found to be involved in modulating protein liquid-liquid phase separation (LLPS), which drives the formation of different membraneless organelles (MLOs). Here, we developed a steric effect-based chemical-enrichment method (SECEM) coupled with liquid chromatography-tandem mass spectrometry to analyze arginine dimethylation (DMA) at the proteome level. We revealed by SECEM that, in mammalian cells, the DMA sites occurring in the RG/RGG motifs are preferentially enriched within the proteins identified in different MLOs, especially stress granules (SGs). Notably, global decrease of protein arginine methylation severely impairs the dynamic assembly and disassembly of SGs. By further profiling the dynamic change of DMA upon SG formation by SECEM, we identified that the most dramatic change of DMA occurs at multiple sites of RG/RGG-rich regions from several key SG-contained proteins, including G3BP1, FUS, hnRNPA1, and KHDRBS1. Moreover, both in vitro arginine methylation and mutation of the identified DMA sites significantly impair LLPS capability of the four different RG/RGG-rich regions. Overall, we provide a global profiling of the dynamic changes of protein DMA in the mammalian cells under different stress conditions by SECEM and reveal the important role of DMA in regulating protein LLPS and SG dynamics.