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Cited by 83RNA Research and SplicingRNA and protein synthesis mechanismsDNA Repair Mechanisms

RNA damage compartmentalization by DHX9 stress granules

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Zhou, Yilong, Panhale, Amol, Shvedunova, Maria, Balan, Mirela, Gomez-Auli, Alejandro, Holz, Herbert, Seyfferth, Janine, Helmstädter, Martin +7 more·2024·Cell
DOI 10.1016/j.cell.2024.02.028
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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.

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  • Melanin-mediated UV resistance stems from a dual mechanism: its conjugated double-bond system efficiently absorbs UV photons, converting them to thermal energy via intramolecular vibration, while its physical architecture scatters incident radiation to reduce cellular penetration.

    “Melanin-mediated UV resistance stems from a dual mechanism: its conjugated double-bond system efficiently absorbs UV photons, converting them to thermal energy via intramolecular vibration, while its physical architecture scatters incident radiation to reduce cellular penetration [76,77].”

    From Fungal Melanin in Plant Pathogens: Complex Biosynthesis Pathways and Diverse Biological Functions (2025) · cites this paper as [76]

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Cited by

Sorted by citations

Authors
Zhou, Y., Panhale, A., Shvedunova, M., Balan, M., Gomez-Auli, A., Holz, H., Seyfferth, J., Helmstädter, M., Kayser, S., Zhao, Y., Erdogdu, N. U., Grzadzielewska, I., Mittler, G., Manke, T., & Akhtar, A.
Affiliations
  • Max Planck Institute of Immunobiology and Epigenetics (DE)
  • University of Freiburg (DE)
Corresponding author
Akhtar, Asifa
ORCID
Venue
Cell
Publisher
Elsevier BV
Published
2024-03
Volume
187
Issue
7
Pages
1701-1718.e28
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2024.02.028
OpenAlex
W4392910961
Cited by
83
References
6
Citations by year
2026: 28 · 2025: 43 · 2024: 12
FWCI
10.74
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Deutsche Forschungsgemeinschaft (CRC 1425 (P04, EXC-2189, CRC 1381, 390939984)
  • European Molecular Biology Organization (RI_00555)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
Keywords
DHX9, stress granules, RNA damage, UV-induced DNA damage, intron splicing, RNA degradation, p62, autophagy receptors
MeSH terms
Stress Granules, Cytoplasm, HeLa Cells, Humans, RNA, RNA, Messenger, Stress, Physiological

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