Lsm7 phase-separated condensates trigger stress granule formation

Author:

Lindström Michelle,Chen LihuaORCID,Jiang ShanORCID,Zhang Dan,Gao Yuan,Zheng Ju,Hao XinxinORCID,Yang Xiaoxue,Kabbinale Arpitha,Thoma JohannesORCID,Metzger Lisa C.ORCID,Zhang Deyuan Y.ORCID,Zhu Xuefeng,Liu HuishengORCID,Gustafsson Claes M.ORCID,Burmann Björn M.ORCID,Winderickx JorisORCID,Sunnerhagen PerORCID,Liu BeidongORCID

Abstract

AbstractStress 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.

Publisher

Springer Science and Business Media LLC

Subject

General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary

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