从5'未翻译区域的翻译塑造了综合应激反应
Shelley R Starck1, Jordan C Tsai2, Keling Chen3
1Department of Biochemistry and Biophysics, Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA. Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA. shelley@walterlab.ucsf.edu nshastri@berkeley.edu peter@walterlab.ucsf.edu.
概括
这项研究表明,BiP mRNA中的上游开放读取 (uORF) 能够在综合应激反应 (ISR) 中实现翻译. 这些uORF产生的可能为免疫系统识别细胞发出信号.
科学领域:
- 分子生物学
- 免疫学
- 细胞生物学
背景情况:
- 在注释编码序列之外的翻译区域是蛋白质组的关键组成部分.
- 在综合应激反应 (ISR) 控制下的mRNA上游开放读取框架 (uORF) 显示特权翻译.
- 这种特权转化发生在细胞启动因子2-三酸盐启动甲基转移RNA (eIF2·GTP·Met-tRNA) 的抑制下.
研究的目的:
- 在ISR期间直接测量uORF翻译产品.
- 在细胞应激过程中调查uORFs在BiPmRNA转化中的作用.
- 探索uORF衍生的的潜在免疫影响.
主要方法:
- 开发一种新的方法,追踪T细胞的翻译,以量化uORF翻译.
- 在BiP mRNA的5'未翻译区域的uORF转化事件的分析.
- 在BiP表达中研究替代启动因子eIF2A和非AUG启动的uORF的要求.
主要成果:
- 在BiP mRNA中识别了来自uORF的标志性翻译事件,这些事件并未在AUG起始码头启动.
- 证明ISR期间的BiP表达依赖于eIF2A和非AUG启动的uORF.
- 观察到持续的uORF转换,保护特定的mRNA免受ISR的影响.
结论:
- 在ISR下,非AUG启动的uORF和eIF2A对BiP mRNA转化至关重要.
- 持续的uORF转换可能会保护特定的mRNA免受ISR诱导的抑制.
- uORF转化产生可以作为MHC I类配体的,可能标记细胞以进行自适应性免疫识别.
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