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

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

doi:10.1126/sciadv.adp5689

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

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

Molecular Neuroscience

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Article number	eadp5689
Journal	Science Advances
Volume	10
Issue number	46
DOIs	https://doi.org/10.1126/sciadv.adp5689
State	Published - Nov 15 2024

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title = "Decoding the interplay between m6A modification and stress granule stability by live-cell imaging",

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.",

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

note = "Publisher Copyright: {\textcopyright} 2024 The Authors, some rights reserved.",

year = "2024",

month = nov,

day = "15",

doi = "10.1126/sciadv.adp5689",

language = "English (US)",

volume = "10",

journal = "Science Advances",

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T1 - Decoding the interplay between m6A modification and stress granule stability by live-cell imaging

AU - Li, Qianqian

AU - Liu, Jian

AU - Guo, Liping

AU - Zhang, Yi

AU - Chen, Yanwei

AU - Liu, Huijuan

AU - Cheng, Hongyu

AU - Deng, Lin

AU - Qiu, Juhui

AU - Zhang, Ke

AU - Goh, Wee Siong Sho

AU - Wang, Yingxiao

AU - Peng, Qin

PY - 2024/11/15

Y1 - 2024/11/15

N2 - 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.

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

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