Lsm7 phase-separated condensates trigger stress granule formation

Michelle Lindström, Lihua Chen (), Shan Jiang, Dan Zhang, Yuan Gao, Ju Zheng, Xinxin Hao, Xiaoxue Yang, Arpitha Kabbinale, Johannes Thoma, Lisa C. Metzger, Deyuan Y. Zhang, Xuefeng Zhu, Huisheng Liu, Claes M. Gustafsson, Björn M. Burmann, Joris Winderickx, Per Sunnerhagen and Beidong Liu ()
Additional contact information
Michelle Lindström: University of Gothenburg
Lihua Chen: University of Gothenburg
Shan Jiang: University of Gothenburg
Dan Zhang: University of Gothenburg
Yuan Gao: University of Gothenburg
Ju Zheng: Functional Biology, KU Leuven
Xinxin Hao: University of Gothenburg
Xiaoxue Yang: University of Gothenburg
Arpitha Kabbinale: University of Gothenburg
Johannes Thoma: University of Gothenburg
Lisa C. Metzger: University of Gothenburg
Deyuan Y. Zhang: Shenyang Aerospace University, Shenbei New District
Xuefeng Zhu: University of Gothenburg
Huisheng Liu: Guangzhou Laboratory
Claes M. Gustafsson: University of Gothenburg
Björn M. Burmann: University of Gothenburg
Joris Winderickx: Functional Biology, KU Leuven
Per Sunnerhagen: University of Gothenburg
Beidong Liu: University of Gothenburg

Nature Communications, 2022, vol. 13, issue 1, 1-17

Abstract: Abstract Stress granules (SGs) are non-membranous organelles facilitating stress responses and linking the pathology of age-related diseases. In a genome-wide imaging-based phenomic screen, we identify Pab1 co-localizing proteins under 2-deoxy-D-glucose (2-DG) induced stress in Saccharomyces cerevisiae. We find that deletion of one of the Pab1 co-localizing proteins, Lsm7, leads to a significant decrease in SG formation. Under 2-DG stress, Lsm7 rapidly forms foci that assist in SG formation. The Lsm7 foci form via liquid-liquid phase separation, and the intrinsically disordered region and the hydrophobic clusters within the Lsm7 sequence are the internal driving forces in promoting Lsm7 phase separation. The dynamic Lsm7 phase-separated condensates appear to work as seeding scaffolds, promoting Pab1 demixing and subsequent SG initiation, seemingly mediated by RNA interactions. The SG initiation mechanism, via Lsm7 phase separation, identified in this work provides valuable clues for understanding the mechanisms underlying SG formation and SG-associated human diseases.

Date: 2022
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DOI: 10.1038/s41467-022-31282-8

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