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哺乳动物tRNA乙化决定了翻译效率和tRNA质量控制

Na Liu^1,2, Bingxue Liu³, Chun-Rui Ma¹

¹State Key Laboratory of RNA Innovation, Science and Engineering, CAS center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.

Nature communications

|July 2, 2025

概括

哺乳动物细胞利用ac4C12RNA修饰来保持翻译效率. 这种修饰的损失会在热应激下触发tRNA的快速衰变,从而揭示出一种新的质量控制途径.

科学领域:

分子生物学分子生物学
在RNA生物学,RNA生物学.
转录后的修改转录后的修改

背景情况:

在C12 (ac4C12) 的tRNA的乙化是一种保存的RNA修饰.
酵母ac4C12在高温下防止tRNA衰变,但其在哺乳动物中的作用尚不清楚.
哺乳动物细胞中快速tRNA衰变 (RTD) 途径的存在尚不清楚.

研究的目的:

为了研究ac4C12在更高的真核生物中的生物功能.
为了确定哺乳动物细胞是否具有RTD通路.
阐明ac4C12在tRNA质量控制和压力下翻译中的作用.

主要方法:

在NIH/3T3细胞中删除Thumpd1,对于ac4C12生物发生是必不可少的.
对tRNA氨基化和转化效率的分析.
在热应激下对tRNA循环的研究.
哺乳动物RTD (mRTD) 机制的特征.

主要成果:

失去了ac4C12降低了tRNA氨基化和翻译效率.
在热应激下,ac4C12低基改导致了选择性快速tRNA^Leu(CAG) 周转.
发现了一种涉及Xrn1/Xrn2和Bpnt1/Bpnt2的哺乳动物RTD通路.

结论:

在哺乳动物细胞中,ac4C12在维持翻译效率方面发挥着至关重要的作用.
哺乳动物细胞具有可热诱导的RTD通路,用于tRNA质量控制.
这项研究揭示了ac4C12和mRTD途径在细胞对热应激反应中的重要性.

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