Time-resolved proteomic profiling reveals compositional and functional transitions across the stress granule life cycle

Shuyao Hu (), Yufeng Zhang, Qianqian Yi, Cuiwei Yang, Yanfen Liu () and Yun Bai ()
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Shuyao Hu: ShanghaiTech University
Yufeng Zhang: ShanghaiTech University
Qianqian Yi: ShanghaiTech University
Cuiwei Yang: ShanghaiTech University
Yanfen Liu: ShanghaiTech University
Yun Bai: ShanghaiTech University

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract Stress granules (SGs) are dynamic, membrane-less organelles. With their formation and disassembly processes characterized, it remains elusive how compositional transitions are coordinated during prolonged stress to meet changing functional needs. Here, using time-resolved proteomic profiling of the acute to prolonged heat-shock SG life cycle, we identify dynamic SG proteins, further segregated into early and late proteins. Comparison of different groups of SG proteins suggests that their biochemical properties help coordinate SG compositional and functional transitions. In particular, early proteins, with high phase-separation-propensity, drive the rapid formation of the initial SG platform, while late proteins are subsequently recruited as discrete modules to further functionalize SGs. This model, supported by immunoblotting and immunofluorescence imaging, provides a conceptual framework for the compositional transitions throughout the acute to prolonged SG life cycle. Additionally, an early SG constituent, non-muscle myosin II, is shown to promote SG formation by increasing SG fusion, underscoring the strength of this dataset in revealing the complexity of SG regulation.

Date: 2023
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DOI: 10.1038/s41467-023-43470-1

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