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Methods to Classify Cytoplasmic Foci as Mammalian Stress Granules
Published on: May 12, 2017
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m6A-binding YTHDF proteins promote stress granule formation
Ye Fu1,2, Xiaowei Zhuang3,4,5
1Howard Hughes Medical Institute, Harvard University, Cambridge, MA, USA.
Nature Chemical Biology
|May 27, 2020
Summary
Messenger RNA (mRNA) methylation, N6-methyladenosine (m6A), and its binding proteins, YTHDF, are crucial for stress granule (SG) assembly. YTHDF proteins regulate SG formation by influencing mRNA recruitment and condensate assembly.
Area of Science:
- Cellular biology
- Molecular biology
- RNA biology
Background:
- Cells form stress granules (SGs) from RNA and proteins during stress.
- The role of N6-methyladenosine (m6A) and its binding proteins in SG assembly is not well understood.
Purpose of the Study:
- To investigate the role of m6A modification and YTHDF proteins in stress granule formation.
- To elucidate the mechanism by which YTHDF proteins regulate SG assembly.
Main Methods:
- Depletion of YTHDF proteins using genetic methods.
- Super-resolution imaging to visualize protein localization and clustering.
- Analysis of mRNA enrichment in SGs.
Main Results:
- m6A-modified mRNAs are enriched in stress granules.
- Depletion of YTHDF1/3 proteins inhibits SG formation and mRNA recruitment.
- YTHDF proteins form clusters and appear to reduce the energy barrier for SG formation.
- Both the disordered N-terminal region and the YTH domain of YTHDF proteins are vital for SG assembly.
Conclusions:
- YTHDF proteins are essential regulators of stress granule formation.
- m6A modification and YTHDF proteins play a significant role in cellular stress response.
- YTHDF proteins may promote SG formation by facilitating condensate assembly.
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