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

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