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Lsm7 phase-separated condensates trigger stress granule formation

Author

Listed:
  • Michelle Lindström

    (University of Gothenburg)

  • Lihua Chen

    (University of Gothenburg
    Guangzhou Laboratory)

  • 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
    University of Gothenburg)

  • Lisa C. Metzger

    (University of Gothenburg
    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
    University of Gothenburg)

  • Joris Winderickx

    (Functional Biology, KU Leuven)

  • Per Sunnerhagen

    (University of Gothenburg)

  • Beidong Liu

    (University of Gothenburg)

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.

Suggested Citation

  • 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 & Huis, 2022. "Lsm7 phase-separated condensates trigger stress granule formation," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31282-8
    DOI: 10.1038/s41467-022-31282-8
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    References listed on IDEAS

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