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血清错误翻译会诱导综合应激反应,而不会积累未充电的tRNAs

Hong Zhang¹, Jiqiang Ling¹

¹Department of Cell Biology and Molecular Genetics, The University of Maryland, College Park, MD 20742, USA.

bioRxiv : the preprint server for biology

|February 19, 2024

概括

氨基酸-tRNA合成酶 (aaRS) 的错误导致Ser的错误整合,构成性地激活了综合应激反应 (ISR). 这种错误翻译,而不是未充电的tRNA,可能会导致核糖体停滞和疾病.

科学领域:

分子生物学分子生物学
细胞生物学细胞生物学
遗传学是一个遗传学.

背景情况:

氨基酸-tRNA合成酶 (aaRSs) 对于精确的蛋白质合成至关重要.
aaRSs中的突变与神经系统疾病和癌症等人类疾病有关.
氨基化错误对细胞应激反应和健康状况的影响尚不清楚.

研究的目的:

为了调查aARSs对细胞应激反应的影响,对aARSs的氨基化错误的影响.
了解通过压力路径将aaRS突变与疾病联系起来的机制.
探索错误翻译在激活综合应激反应 (ISR) 中的作用.

主要方法:

分析了Ser被错误地纳入Ala和Thr编码子的影响.
研究aARS编辑缺陷和tRNA突变的作用.
评估独立于未充电tRNA积累的ISR激活.
检查因错误翻译而导致的潜在核糖体停滞和碰撞.

主要成果:

错误地将Ser纳入Ala和Thr编码子,构成性地激活了ISR.
ISR激活发生的独立于未充电的tRNA积累.
错误翻译,而不是未充电的tRNA,似乎是ISR激活的触发因素.
有证据表明,错误翻译可能导致核糖体停滞和碰撞.

结论:

氨基化错误,特别是Ser错误整合,可以长期激活ISR.
慢性ISR激活与疾病的发病有关,包括神经病变.
对错误翻译诱导的核糖体动力学的进一步研究是有必要的.

关键词:

在 AlaRS 的基础上,这就是ThrRSRS的意思.翻译忠实性翻译忠实性在tRNA的错误结合过程中.

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