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Journal Article

RNA damage compartmentalization by DHX9 stress granules

MPS-Authors

Zhou,  Yilong
Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Panhale,  Amol
Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Shvedunova,  Maria
Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Balan,  Mirela
Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Gomez-Auli,  Alejandro
Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Holz,  Herbert
Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Seyfferth,  Janine
Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Zhao,  Yuling
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, International Max Planck Research School for Immunobiology, Epigenetics, and Metabolism (IMPRS-IEM);

Erdogdu,  Niyazi Umut
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, International Max Planck Research School for Immunobiology, Epigenetics, and Metabolism (IMPRS-IEM);

Grzadzielewska,  Iga
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, International Max Planck Research School for Immunobiology, Epigenetics, and Metabolism (IMPRS-IEM);

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Mittler,  Gerhard
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Manke,  Thomas
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Akhtar,  Asifa
Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

External Resource

https://www.sciencedirect.com/science/article/pii/S0092867424002319?via%3Dihub
(Publisher version)

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Fulltext (public)

10.1016_j.cell.2024.02.028.pdf
(Publisher version), 24MB

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Citation

Zhou, Y., Panhale, A., Shvedunova, M., Balan, M., Gomez-Auli, A., Holz, H., et al. (2024). RNA damage compartmentalization by DHX9 stress granules. Cell, 187, 1701-1718. doi:10.1016/j.cell.2024.02.028.


Cite as: https://hdl.handle.net/21.11116/0000-000F-3944-5
Abstract
Biomolecules incur damage during stress conditions, and damage partitioning represents a vital survival strategy for cells. Here, we identified a distinct stress granule (SG), marked by dsRNA helicase DHX9, which compartmentalizes ultraviolet (UV)-induced RNA, but not DNA, damage. Our FANCI technology revealed that DHX9 SGs are enriched in damaged intron RNA, in contrast to classical SGs that are composed of mature mRNA. UV exposure causes RNA crosslinking damage, impedes intron splicing and decay, and triggers DHX9 SGs within daughter cells. DHX9 SGs promote cell survival and induce dsRNA-related immune response and translation shutdown, differentiating them from classical SGs that assemble downstream of translation arrest. DHX9 modulates dsRNA abundance in the DHX9 SGs and promotes cell viability. Autophagy receptor p62 is activated and important for DHX9 SG disassembly. Our findings establish non-canonical DHX9 SGs as a dedicated non-membrane-bound cytoplasmic compartment that safeguards daughter cells from parental RNA damage.