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<p>Methyltransferase 1 (METTL1) is currently regarded as a key tRNA m<sup>7</sup>G writer. Recent studies indicate its potential role in carcinogenesis via increased m<sup>7</sup>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<sup>7</sup>G modification, but also enhances expression of one m<sup>7</sup>G-modified tiRNA, m<sup>7</sup>G-3'&#xa0;tiRNA-Met<sup>CAT</sup> (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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月5日

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  • Wenyu Hu,
  • Yaomin Liang,
  • Xiaoling Ying,
  • Yapeng Huang,
  • Chang Xiong,
  • Bixia Liu,
  • Yifan Lv,
  • Cong Chen,
  • Chengcheng Zhang,
  • Haiqing Zhang,
  • Hu Li,
  • Mei Yang,
  • Weidong Ji

摘要

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-MetCAT (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.