转移RNA乙化在体内调节哺乳动物的压力信号
Supuni Thalalla Gamage1, Roxane Khoogar2, Shereen Howpay Manage1
1Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD, USA.
Science advances
|March 19, 2025
概括
转移RNA (tRNA) 乙化,由Nat10和Thumpd1调节,影响tRNA水平,核糖体停滞和压力信号. 在小鼠中失去这种修饰会导致生长缺陷和致命性,这揭示了它在哺乳动物转化中的关键作用.
科学领域:
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
- 生物化学 生化学
背景情况:
- 转移RNA (tRNA) 修改对于精确的蛋白质合成至关重要.
- 特定tRNA修饰的生理作用,如N4-乙基丁 (ac4C),尚未完全理解.
- Nat10是一种必不可少的酶,可催化tRNA上的ac4C修饰.
研究的目的:
- 为了研究ac4CtRNA修饰的生理影响.
- 为了探索Thumpd1的作用,一个适配蛋白 Nat10,在tRNA乙化.
- 确定受损tRNA乙化对细胞过程和生物体健康的影响.
主要方法:
- 使用了针对Thumpd1和Gcn2.2的淘汰赛小鼠模型.
- 评估了tRNA水平,核糖体停滞和eIF2α酸化.
- 观察到的表型结果包括生长,生育和生存率.
主要成果:
- 丢失Thumpd1导致tRNA水平降低,并增加了核糖体停滞.
- 损伤的tRNA乙化激活了eIF2α酸化,一种应激反应.
- Thumpd1的淘汰赛小鼠表现出生长缺陷和不育.
- 双重淘汰Thumpd1和Gcn2导致严重的产后死亡.
结论:
- 细胞质tRNAs上的ac4C修饰对于调节核糖体介导的压力信号至关重要.
- 这种tRNA修饰在哺乳动物发育和生理学中起着重要作用.
- 结果提供了对转化控制和潜在治疗点的见解.
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