Abstract
Methyltransferase 1 (METTL1) is currently regarded as a key tRNA m(7)G writer. Recent studies indicate its potential role in carcinogenesis via increased m(7)G 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 m(7)G modification, but also enhances expression of one m(7)G-modified tiRNA, m(7)G-3' tiRNA-Met(CAT) (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.