March 28, 2024 | Yilong Zhou, Amol Panhale, Maria Shvedunova, Mirela Balan, Alejandro Gomez-Auli, Herbert Holz, Janine Seyfferth, Martin Helmstaedter, Séverine Kayser, Yuling Zhao, Niyazi Umut Erdogdu, Iga Grzadzielewska, Gerhard Mittler, Thomas Manke, Asifa Akhtar
RNA damage compartmentalization by DHX9 stress granules
UV-induced RNA, but not DNA, crosslinking damage triggers DHX9 stress granules (SGs) specifically in daughter cells. These SGs are enriched in damaged intron RNA and activate stress responses, protecting daughter cells from parental RNA damage. DHX9 SGs differ from classical SGs by inducing dsRNA-related immune responses and translation shutdown, rather than being a consequence of translation arrest. DHX9 modulates dsRNA abundance in SGs and promotes cell survival. Autophagy receptor p62 is involved in SG disassembly. DHX9 SGs are non-canonical, non-membrane-bound cytoplasmic compartments that safeguard daughter cells from parental RNA damage. The study reveals that UV-induced RNA crosslinking damage leads to DHX9 SG formation, which sequesters damaged intron RNA and activates immune responses. DHX9 SGs are distinct from classical SGs in their composition and function, and their assembly is crucial for protecting daughter cells from RNA damage. The findings highlight the role of DHX9 in stress response and RNA damage repair.RNA damage compartmentalization by DHX9 stress granules
UV-induced RNA, but not DNA, crosslinking damage triggers DHX9 stress granules (SGs) specifically in daughter cells. These SGs are enriched in damaged intron RNA and activate stress responses, protecting daughter cells from parental RNA damage. DHX9 SGs differ from classical SGs by inducing dsRNA-related immune responses and translation shutdown, rather than being a consequence of translation arrest. DHX9 modulates dsRNA abundance in SGs and promotes cell survival. Autophagy receptor p62 is involved in SG disassembly. DHX9 SGs are non-canonical, non-membrane-bound cytoplasmic compartments that safeguard daughter cells from parental RNA damage. The study reveals that UV-induced RNA crosslinking damage leads to DHX9 SG formation, which sequesters damaged intron RNA and activates immune responses. DHX9 SGs are distinct from classical SGs in their composition and function, and their assembly is crucial for protecting daughter cells from RNA damage. The findings highlight the role of DHX9 in stress response and RNA damage repair.