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

• 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
• 来源期刊: 科学通报（英文版）
• 年，卷（期）: 2021,（13）
• 所属期刊栏目: ARTICLES
• 页码范围: 1342-1357
• 页数: 16页
• 语种: 英文

摘要

Thousands of proteins undergo arginine methylation,a widespread post-translational modification cat-alyzed 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 ribo-some 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.