德国马克斯·普朗克免疫生物学和表观遗传学研究所Asifa Akhtar团队近期取得重要工作进展，他们研究提出了DHX9应激颗粒对损伤RNA的区室化作用。相关研究成果2024年3月18日在线发表于《细胞》杂志上。

据介绍，生物分子在应激条件下会受到损伤，而损伤分配代表了细胞的重要生存策略。

研究人员鉴定了一种独特的应激颗粒（SG），以dsRNA解旋酶DHX9为标志，它将紫外线（UV）诱导的RNA而非DNA损伤区分开。FANCI技术显示，与由成熟mRNA组成的经典SG相比，DHX9 SG富含受损的内含子RNA。紫外线暴露会导致RNA交联损伤，阻碍内含子剪接和衰变，并在子细胞内触发DHX9 SG。

DHX9 SG促进细胞存活，诱导dsRNA相关的免疫反应和翻译关闭，将其与在翻译停滞下游组装的经典SG区分开来。DHX9调节DHX9 SG中的dsRNA丰度并促进细胞活力。自噬受体p62被激活并且对于DHX9 SG的分解是重要的。

总之，这一发现将非经典DHX9 SG确立为一个专门的非膜结合细胞质区室，保护子细胞免受亲本RNA损伤。

附：英文原文

Title: RNA damage compartmentalization by DHX9 stress granules

Author: Yilong Zhou, Amol Panhale, Maria Shvedunova, Mirela Balan, Alejandro Gomez-Auli, Herbert Holz, Janine Seyfferth, Martin Helmstdter, Séverine Kayser, Yuling Zhao, Niyazi Umut Erdogdu, Iga Grzadzielewska, Gerhard Mittler, Thomas Manke, Asifa Akhtar

Issue&Volume: 2024-03-18

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.

DOI: 10.1016/j.cell.2024.02.028

Source: https://www.cell.com/cell/fulltext/S0092-8674(24)00231-9