线粒体双链RNA在人类中触发抗病毒信号
Ashish Dhir1, Somdutta Dhir2, Lukasz S Borowski3,4
1Sir William Dunn School of Pathology, University of Oxford, Oxford, UK. ashish.dhir@path.ox.ac.uk.
Nature
|July 27, 2018
概括
研究人员在细胞中发现了不稳定的线粒体双链RNA. 关键酶SUV3和多核酸酶 (PNPase) 限制其水平,防止免疫激活.
科学领域:
- 细胞生物学
- 免疫学
- 分子生物学
背景情况:
- 线粒体起源于内共生细菌,具有循环基因组,可以进行双向转录.
- 哺乳动物的这一过程可以产生重叠的转录,可能形成双链RNA (dsRNA).
- 线粒体dRNA的体内存在和功能在很大程度上没有被描述.
研究的目的:
- 在体内特征原生线粒体双链RNA.
- 确定参与调节线粒体dRNA水平的细胞因素.
- 研究线粒体dRNA与先天免疫激活之间的联系.
主要方法:
- 单细胞分析检测线粒体dRNA.
- 在小鼠中对线粒体RNA酶SUV3和多核酸酶 (PNPase) 的基因操纵.
- 免疫信号通路的分析,包括MDA5和I型干扰素反应.
- 来自PNPT1突变患者的临床数据分析.
主要成果:
- 在单细胞水平上检测到一种高度不稳定的原生线粒体dRNA物种.
- SUV3或PNPase的损失导致了线粒体dRNA的显著积累.
- 线粒体dRNA进入细胞质,激活MDA5并触发I型干扰素反应.
- 患有PNPT1突变的患者表现出线粒体dRNA积累和免疫激活标记.
结论:
- SUV3和PNP酶对于限制线粒体dRNA水平和防止其细胞质释放至关重要.
- 在线粒体内的线粒体dRNA管理中,PNPase起着双重作用.
- 线粒体dRNA积累可以不适当地激活先天免疫防御,模仿病毒感染.
- 线粒体dRNA处理的失调与人体免疫障碍有关.
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