Decoding the interplay between m6A modification and stress granule stability by live-cell imaging

IF 11.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Science Advances Pub Date : 2024-11-15 DOI:10.1126/sciadv.adp5689

Qianqian Li, Jian Liu, Liping Guo, Yi Zhang, Yanwei Chen, Huijuan Liu, Hongyu Cheng, Lin Deng, Juhui Qiu, Ke Zhang, Wee Siong Sho Goh, Yingxiao Wang, Qin Peng

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Abstract

N⁶-methyladenosine (m⁶A)–modified mRNAs and their cytoplasmic reader YTHDFs are colocalized with stress granules (SGs) under stress conditions, but the interplay between m⁶A modification and SG stability remains unclear. Here, we presented a spatiotemporal m⁶A imaging system (SMIS) that can monitor the m⁶A modification and the translation of mRNAs with high specificity and sensitivity in a single live cell. SMIS showed that m⁶A-modified reporter mRNAs dynamically enriched into SGs under arsenite stress and gradually partitioned into the cytosol as SG disassembled. SMIS revealed that knockdown of YTHDF2 contributed to SG disassembly, resulting in the fast redistribution of mRNAs from SGs and rapid recovery of stalled translation. The mechanism is that YTHDF2 can regulate SG stability through the interaction with G3BP1 in m⁶A-modified RNA-dependent manner. Our results suggest a mechanism for the interplay between m⁶A modification and SG through YTHDF2 regulation.

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通过活细胞成像解码 m 6 A 修饰与应力颗粒稳定性之间的相互作用

N 6 -甲基腺苷（m 6 A）修饰的mRNA及其胞质阅读器YTHDFs在应激条件下与应激颗粒（SG）共定位，但m 6 A修饰与SG稳定性之间的相互作用仍不清楚。在这里，我们展示了一种时空 m 6 A 成像系统（SMIS），它能在单个活细胞中以高特异性和高灵敏度监测 m 6 A 修饰和 mRNA 的翻译。SMIS显示，在亚砷酸盐胁迫下，m 6 A修饰的报告基因mRNA动态地富集到SG中，并随着SG的解体逐渐进入细胞质。SMIS发现，YTHDF2的敲除有助于SG的解体，导致mRNA从SG中快速重新分布，并使停滞的翻译迅速恢复。其机制是YTHDF2通过与G3BP1相互作用，以m 6 A修饰RNA依赖的方式调节SG的稳定性。我们的研究结果表明，m 6 A修饰与SG之间的相互作用机制是通过YTHDF2调控的。

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来源期刊

Science Advances 综合性期刊-综合性期刊

CiteScore

21.40

自引率

1.50%

发文量

1937

审稿时长

29 weeks

期刊介绍： Science Advances, an open-access journal by AAAS, publishes impactful research in diverse scientific areas. It aims for fair, fast, and expert peer review, providing freely accessible research to readers. Led by distinguished scientists, the journal supports AAAS's mission by extending Science magazine's capacity to identify and promote significant advances. Evolving digital publishing technologies play a crucial role in advancing AAAS's global mission for science communication and benefitting humankind.