Abstract

N⁶-methyladenosine (m⁶A)–modified mRNAs and their cytoplasmic reader YTHDFs are colocalized with stress granules (SGs) under stress conditions, but the interplay betweenm⁶A modification and SG stability remains unclear. Here, we presented a spatiotemporalm⁶A imaging system (SMIS) that can monitor them⁶A modification and the translation of mRNAs with high specificity and sensitivity in a single live cell. SMIS showed thatm⁶A-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 inm⁶A-modified RNA-dependent manner. Our results suggest a mechanism for the interplay betweenm⁶A modification and SG through YTHDF2 regulation.

Title

Decoding the interplay betweenm⁶A modification and stress granule stability by live-cell imaging

Authors

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, and Qin Peng

Journal Information

Science Advances (2024)

DOI

DOI: 10.1126/sciadv.adp5689

View at publisher↗