Institute of Molecular Biology and Genetics, Aarhus University, 8000, Aarhus, Denmark.
Institute of Biomedicine and Translational Medicine, University of Tartu, 50411, Tartu, Estonia.
EMBO Rep. 2024 Apr;25(4):1814-1834. doi: 10.1038/s44319-024-00098-6. Epub 2024 Feb 27.
Stress granules are an integral part of the stress response that are formed from non-translating mRNAs aggregated with proteins. While much is known about stress granules, the factors that drive their mRNA localization are incompletely described. Modification of mRNA can alter the properties of the nucleobases and affect processes such as translation, splicing and localization of individual transcripts. Here, we show that the RNA modification N4-acetylcytidine (ac4C) on mRNA associates with transcripts enriched in stress granules and that stress granule localized transcripts with ac4C are specifically translationally regulated. We also show that ac4C on mRNA can mediate localization of the protein NOP58 to stress granules. Our results suggest that acetylation of mRNA regulates localization of both stress-sensitive transcripts and RNA-binding proteins to stress granules and adds to our understanding of the molecular mechanisms responsible for stress granule formation.
应激颗粒是应激反应的一个组成部分，由与蛋白质聚集的非翻译 mRNA 组成。虽然人们对应激颗粒有了很多了解，但驱动其 mRNA 定位的因素描述得还不完全清楚。mRNA 的修饰可以改变核碱基的性质，并影响翻译、剪接和单个转录本的定位等过程。在这里，我们表明 mRNA 上的 RNA 修饰 N4-乙酰胞嘧啶 (ac4C) 与富含应激颗粒的转录本相关，并且具有 ac4C 的应激颗粒定位转录本受到特异性翻译调控。我们还表明，mRNA 上的 ac4C 可以介导蛋白 NOP58 向应激颗粒的定位。我们的结果表明，mRNA 的乙酰化调节应激敏感转录本和 RNA 结合蛋白向应激颗粒的定位，这增加了我们对负责应激颗粒形成的分子机制的理解。
