SARS-CoV-2 RNA 稳定了宿主 mRNA,从而引起了免疫病原发生
Hailian Zhao1, Zhaokui Cai2, Jian Rao3
1Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
Molecular cell
|December 21, 2023
概括
SARS-CoV-2 RNA 劫持宿主 RNA,形成重复体以增加 mRNA 稳定性并促进严重的 COVID-19. 针对这些RNA-RNA相互作用或YBX3蛋白可能为抗病毒提供新的治疗策略.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 2019年严重的冠状病毒病 (COVID-19) 是由SARS-CoV-2RNA相互作用驱动的,这些相互作用抑制干扰素反应并诱导细胞因子的释放.
- 目前尚不完全了解SARS-CoV-2操纵宿主RNA引起不平衡免疫反应的精确机制.
研究的目的:
- 研究感染细胞和患者样本中SARS-CoV-2RNA结构和与宿主因子的相互作用.
- 阐明SARS-CoV-2RNA结合如何影响宿主mRNA稳定性和免疫信号传递.
- 确定针对COVID-19的治疗干预的潜在宿主目标.
主要方法:
- 在感染细胞和患者肺样本中使用RIC-seq分析了in situ的RNA相互作用.
- 研究了RNA结合蛋白YBX3在调解SARS-CoV-2RNA与宿主mRNA相互作用中的作用.
- 进行了淘汰实验和RNA复合体的破坏,以评估功能后果.
主要成果:
- SARS-CoV-2 RNA与205个宿主mRNA形成了广泛的重复,通过YBX3招募增加了它们的稳定性.
- 破坏这些RNA-RNA相互作用或YBX3敲击降低了宿主mRNA的稳定性和病毒复制.
- 由SARS-CoV-2稳定的主体基因NFKBIZ被发现促进细胞因子的产生并抑制干扰素反应,从而导致细胞因子风暴.
结论:
- SARS-CoV-2利用RNA-RNA相互作用来稳定宿主mRNA,调节免疫反应,并促进严重的COVID-19.
- YBX3和特定宿主mRNA点代表了SARS-CoV-2病变发生过程中的关键参与者.
- 这些发现突出了RNA-RNA相互作用作为病毒免疫病原发生的关键机制,并为药物开发提供了潜在的治疗点.
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