m3C32 tRNA modification controls serine codon-biased mRNA translation, cell cycle, and DNA-damage response

文献类型： 外文期刊

第一作者： Cui, Jia

作者： Cui, Jia;Sendinc, Erdem;Liu, Qi;Kim, Sujin;Fang, Jaden Y.;Gregory, Richard I.;Cui, Jia;Sendinc, Erdem;Liu, Qi;Kim, Sujin;Fang, Jaden Y.;Gregory, Richard I.;Liu, Qi;Liu, Qi;Gregory, Richard I.;Gregory, Richard I.;Gregory, Richard I.

作者机构：

期刊名称：NATURE COMMUNICATIONS （ 影响因子：14.7； 五年影响因子：16.1 ）

ISSN：

年卷期： 2024 年 15 卷 1 期

页码：

收录情况： SCI

摘要： The epitranscriptome includes a diversity of RNA modifications that influence gene expression. N3-methylcytidine (m(3)C) mainly occurs in the anticodon loop (position C32) of certain tRNAs yet its role is poorly understood. Here, using HAC-Seq, we report comprehensive METTL2A/2B-, METTL6-, and METTL2A/2B/6-dependent m(3)C profiles in human cells. METTL2A/2B modifies tRNA-arginine and tRNA-threonine members, whereas METTL6 modifies the tRNA-serine family. However, decreased m(3)C32 on tRNA-Ser-GCT isodecoders is only observed with combined METTL2A/2B/6 deletion. Ribo-Seq reveals altered translation of genes related to cell cycle and DNA repair pathways in METTL2A/2B/6-deficient cells, and these mRNAs are enriched in AGU codons that require tRNA-Ser-GCT for translation. These results, supported by reporter assays, help explain the observed altered cell cycle, slowed proliferation, and increased cisplatin sensitivity phenotypes of METTL2A/2B/6-deficient cells. Thus, we define METTL2A/2B/6-dependent methylomes and uncover a particular requirement of m(3)C32 tRNA modification for serine codon-biased mRNA translation of cell cycle, and DNA repair genes.

分类号：

  • 相关文献
作者其他论文 更多>>

微信小程序