美国哈佛大学Wenyi Wei等研究人员合作发现，PRMT1与SAMTOR相互配合通过NPRL2的精氨酸甲基化调节mTORC1的蛋氨酸感应。这一研究成果于2023年11月24日发表在国际顶尖学术期刊《细胞—代谢》上。

研究人员报告了PRMT1通过利用SAM作为辅因子来感知蛋氨酸/SAM，从而对mTORC1信号转导进行基于酶活性的调节。在蛋氨酸充足的条件下，细胞膜SAM的升高会从GATOR1中释放出SAMTOR，从而使PRMT1与GATOR1结合。随后，加载了SAM的PRMT1会甲基化GATOR1的催化亚基NPRL2，从而抑制其GAP活性，导致mTORC1激活。值得注意的是，遗传或药物抑制PRMT1会阻碍mTORC1对肝脏蛋氨酸的感应，并改善老年小鼠对胰岛素的敏感性，从而确定PRMT1介导的蛋氨酸感应在生理水平上的作用。因此，PRMT1与SAMTOR相互配合，构成了mTORC1信号传导的蛋氨酸感应装置。

据了解，蛋氨酸是决定mTORC1激活的多种营养输入的一个重要分支。在缺乏蛋氨酸的情况下，SAMTOR与GATOR1结合并抑制mTORC1信号传导。然而，mTORC1在蛋氨酸刺激下如何被激活在很大程度上仍是一个谜。

附：英文原文

Title: PRMT1 orchestrates with SAMTOR to govern mTORC1 methionine sensing via Arg-methylation of NPRL2

Author: Cong Jiang, Jing Liu, Shaohui He, Wei Xu, Runzhi Huang, Weijuan Pan, Xiaolong Li, Xiaoming Dai, Jianping Guo, Tao Zhang, Hiroyuki Inuzuka, Ping Wang, John M. Asara, Jianru Xiao, Wenyi Wei

Issue&Volume: 2023-11-24

Abstract: Methionine is an essential branch of diverse nutrient inputs that dictate mTORC1 activation.In the absence of methionine, SAMTOR binds to GATOR1 and inhibits mTORC1 signaling.However, how mTORC1 is activated upon methionine stimulation remains largely elusive.Here, we report that PRMT1 senses methionine/SAM by utilizing SAM as a cofactor foran enzymatic activity-based regulation of mTORC1 signaling. Under methionine-sufficientconditions, elevated cytosolic SAM releases SAMTOR from GATOR1, which confers theassociation of PRMT1 with GATOR1. Subsequently, SAM-loaded PRMT1 methylates NPRL2,the catalytic subunit of GATOR1, thereby suppressing its GAP activity and leadingto mTORC1 activation. Notably, genetic or pharmacological inhibition of PRMT1 impedeshepatic methionine sensing by mTORC1 and improves insulin sensitivity in aged mice,establishing the role of PRMT1-mediated methionine sensing at physiological levels.Thus, PRMT1 coordinates with SAMTOR to form the methionine-sensing apparatus of mTORC1signaling.

DOI: 10.1016/j.cmet.2023.11.001

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00411-4