細胞は日焼けから身を守る機能を受け継ぐ(Cells inherit protection from sunburn)

2024-03-19

2024-03-18 マックス・プランク研究所

ドイツのフライブルクにあるマックス・プランク免疫生物学・エピジェネティクス研究所の研究チームは、紫外線によって引き起こされるRNAの損傷から細胞を守る細胞シールドを発見しました。細胞が分裂すると、母細胞から防御システムが娘細胞に受け継がれ、特殊なストレス顆粒が形成されます。このシステムは、酵素DHX9によって形成される特別なストレス顆粒によって損傷したRNAを捕捉し、新しい細胞を健康に保ちます。UV放射線はDNAだけでなくRNAも損傷し、母細胞からのDHX9タンパク質がストレス顆粒を形成して損傷したRNAを隔離し、娘細胞を保護します。

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DHX9ストレス顆粒によるRNA損傷のコンパートメント化 RNA damage compartmentalization by DHX9 stress granules

Yilong Zhou,Amol Panhale,Maria Shvedunova,…,Gerhard Mittler,Thomas Manke,Asifa Akhtar
Cell Published:March 18, 2024
DOI:https://doi.org/10.1016/j.cell.2024.02.028

Highlights

•UV-induced RNA, but not DNA, crosslinking damage induces DHX9 SGs

•Cytoplasmic DHX9 SGs are enriched in damaged intron RNA

•DHX9 SGs activate multiple stress responses in daughter cells

•DHX9 SGs protect daughter cells from parental RNA damage

Summary

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.