RNA damage compartmentalization by DHX9 stress granules

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

Standort
Deutsche Nationalbibliothek Frankfurt am Main
Umfang
Online-Ressource
Sprache
Englisch
Anmerkungen
Cell. - 187, 7 (2024) , 1701-1718.e28, ISSN: 1097-4172

Klassifikation
Medizin, Gesundheit

Ereignis
Veröffentlichung
(wo)
Freiburg
(wer)
Universität
(wann)
2024
Urheber
Zhou, Yilong
Panhale, Amol
Shvedunova, Maria
Bãlan, Mirela
Gómez Aulí, Alejandro
Holz, Herbert
Seyfferth, Janine
Helmstädter, Martin
Kayser, Séverine
Zhao, Yuling
Erdogdu, Niyazi Umut
Grzadzielewska, Iga
Mittler, Gerhard
Manke, Thomas
Akhtar, Asifa

DOI
10.1016/j.cell.2024.02.028
URN
urn:nbn:de:bsz:25-freidok-2466173
Rechteinformation
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Letzte Aktualisierung
25.03.2025, 13:42 MEZ

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Entstanden

  • 2024

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