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Visualization of G3BP Stress Granules Dynamics in Live Primary Cells

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Published on: May 21, 2014

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

Qianqian Li¹, Jian Liu¹, Liping Guo^1,2

¹Shenzhen Bay Laboratory, Shenzhen 518132, China.

Science Advances

|November 15, 2024

Summary

N6-methyladenosine (m6A) modification and its reader YTHDF2 regulate stress granule (SG) stability. YTHDF2

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Area of Science:

Molecular Biology
Cell Biology
RNA Biology

Background:

N6-methyladenosine (m6A) modification and its cytoplasmic reader proteins, YTHDFs, are known to interact with stress granules (SGs).
The precise role of m6A modification and YTHDF proteins in regulating SG dynamics and mRNA translation under stress remains largely uncharacterized.

Purpose of the Study:

To investigate the interplay between m6A modification and stress granule stability.
To elucidate the mechanism by which YTHDF proteins influence SG dynamics and mRNA translation recovery.

Main Methods:

Development and application of a spatiotemporal m6A imaging system (SMIS) for live-cell monitoring of m6A modification and mRNA translation.
Utilizing SMIS to observe dynamic changes in m6A-modified mRNAs within SGs under arsenite stress.
Employing knockdown of YTHDF2 to assess its impact on SG disassembly and mRNA redistribution.

Main Results:

SMIS demonstrated dynamic enrichment of m6A-modified mRNAs into SGs under arsenite stress, followed by partitioning into the cytosol upon SG disassembly.
Knockdown of YTHDF2 accelerated SG disassembly, leading to faster mRNA redistribution and recovery of stalled translation.
YTHDF2 was found to regulate SG stability via interaction with G3BP1 in an m6A-modified RNA-dependent manner.

Conclusions:

m6A modification and YTHDF2 play a crucial role in regulating stress granule stability.
YTHDF2's interaction with G3BP1, dependent on m6A-modified RNA, mediates SG stability and translation recovery.
This study reveals a novel mechanism linking m6A modification to stress granule dynamics and translational control.