Hu Wenyu, Liang Yaomin, Ying Xiaoling, Huang Yapeng, Xiong Chang, Liu Bixia, Lv Yifan, Chen Cong, Zhang Chengcheng, Zhang Haiqing, Li Hu, Yang Mei, Ji Weidong
Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-Sen University , Guangzhou, 510080, China.
Department of Urology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510220, China.
Cell Biol Toxicol. 2025 Aug 5;41(1):124. doi: 10.1007/s10565-025-10072-0.
Methyltransferase 1 (METTL1) is currently regarded as a key tRNA mG writer. Recent studies indicate its potential role in carcinogenesis via increased mG modification to stabilize tRNA and upregulate tRNA expression. Cadmium-induced stress triggers the assembly of stress granules (SGs) and production of tRNA-derived stress-induced RNAs (tiRNAs). However, whether METTL1 is involved in the formation of cadmium-induced SGs and its mechanism are still unclear. Here, we demonstrated that METTL1 promotes cadmium-induced SGs formation. Mechanistically, METTL1 not only upregulates SG's core protein Ras-GTPase-activating protein SH3 domain-binding protein 1 (G3BP1) translation through tRNAs mG modification, but also enhances expression of one mG-modified tiRNA, mG-3' tiRNA-Met (mtiRM), which affects SGs assembly. Together, the findings concluded that the promotional effect of METTL1 on cadmium-induced SGs formation jointly through G3BP1 translation and mtiRM expression, thus providing insights into an intimate link between SGs and tumorigenesis.
甲基转移酶1（METTL1）目前被视为关键的tRNA mG书写蛋白。近期研究表明，它可能通过增加mG修饰来稳定tRNA并上调tRNA表达，从而在致癌过程中发挥作用。镉诱导的应激会触发应激颗粒（SGs）的组装以及tRNA衍生的应激诱导RNA（tiRNAs）的产生。然而，METTL1是否参与镉诱导的SGs形成及其机制仍不清楚。在此，我们证明METTL1促进镉诱导的SGs形成。机制上，METTL1不仅通过tRNAs mG修饰上调SG的核心蛋白Ras-GTP酶激活蛋白SH3结构域结合蛋白1（G3BP1）的翻译，还增强一种mG修饰的tiRNA，即mG-3' tiRNA-Met（mtiRM）的表达，而mtiRM会影响SGs的组装。总之，这些发现表明METTL1通过G3BP1翻译和mtiRM表达共同促进镉诱导的SGs形成，从而为SGs与肿瘤发生之间的密切联系提供了见解。
