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由IRE1α产生的5'-tRNAGly(GCC)半部分与ER应激反应有关
Hanyong Jin1, Ji-Hyun Yeom2,3, Eunkyoung Shin2,4
1Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, 133002, Jilin, China.
Nature communications
|October 29, 2024
概括
需要内醇的酶1α (IRE1α) 在内质网膜应激过程中产生5'-tRH-GlyGCC. 这种分子促进癌细胞增殖和mRNA调节,表明在细胞适应中具有进化保存的作用.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生物化学
背景情况:
- 转移RNA半体 (tRHs) 有不同的生物作用,但它们的特定生物发生途径仍然不清楚.
- 细胞内膜网膜 (ER) 压力是一种关键的细胞状况,影响蛋白质稳态和细胞命运.
研究的目的:
- 在ER压力条件下阐明特定5RHs的生物发生.
- 研究5RH-GlyGCC在细胞过程中的功能和调节,包括癌症增殖和mRNA异形调节.
主要方法:
- 研究了需要伊诺西的酶1α (IRE1α) 在tRNAGly(GCC)上的分裂活性.
- 利用体外和体内模型来评估5RH-GlyGCC对细胞增殖和mRNA生物发生的影响.
- 通过联合表达研究确定了5RH-GlyGCC的结合蛋白.
- 在ER压力下检查了小鼠器官和*Cryptococcus neoformans*中的IRE1α和5RH-GlyGCC的表达.
主要成果:
- 在ER应激时,IRE1α选择性地分裂tRNA (Gly) 来产生5RH-Gly (GCC).
- 5RH-GlyGCC水平与癌细胞增殖有积极的相关性,并调节mRNA异形生物发生.
- 鉴定出HNRNPM和HNRNPH2是5RH-GlyGCC功能必不可少的结合蛋白.
- 在ER压力下,在小鼠器官和*C. neoformans*中观察到IRE1α和5RH-GlyGCC的同时诱导.
结论:
- IRE1α介导的5RH-GlyGCC生成是一种在ER压力期间产生功能性tRH的新途径.
- 5 RH-GlyGCC在癌细胞增殖和mRNA调节中起着重要作用,需要HNRNPM和HNRNPH2.
- 这些发现表明IRE1α生成的5RH-Gly在细胞适应ER压力的过程中具有进化保守的作用.
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