METTL1 promotes cadmium-induced stress granules formation via enhancing translation of G3BP1 and expression of m7G- 3' tiRNA MetCAT.

Methyltransferase 1 (METTL1) is currently regarded as a key tRNA m⁷G writer. Recent studies indicate its potential role in carcinogenesis via increased m⁷G 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 m⁷G modification, but also enhances expression of one m⁷G-modified tiRNA, m⁷G-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.