SARS-CoV-2的RNA-依赖RNA聚合酶通过劫持eEF1A因素来调节宿主mRNA的翻译效率
Haili Gan1, Xiaoguang Zhou2, Qiong Lei2
1Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 201204, China.
Biochimica et biophysica acta. Molecular basis of disease
|September 6, 2023
概括
SARS-CoV-2 NSP12 蛋白质结合宿主RNA并劫持eEF1A因子以抑制干扰素的产生和改变宿主mRNA转化,提供潜在的药物标.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 宿主-病原体相互作用
背景情况:
- 在SARS-CoV-2的RNA依赖RNA聚合酶 (NSP12) 对于病毒复制至关重要.
- 它在调节宿主细胞功能中的作用仍然在很大程度上是未知的.
研究的目的:
- 为了研究SARS-CoV-2 NSP12在宿主细胞中的非复制功能.
- 阐明NSP12影响宿主基因表达和细胞过程的机制.
主要方法:
- 个人-CLIP (iCLIP) 技术用于识别NSP12.的宿主RNA结合部位.
- 同免疫沉和细胞局部化研究,以评估蛋白质-蛋白质相互作用.
- 核糖体概况和西部抹杀分析宿主mRNA翻译效率和蛋白质水平.
主要成果:
- NSP12通过一种保存的基因结合宿主RNA,特别是核糖体RNA.
- NSP12与宿主因子eEF1A直接相互作用,抑制I型干扰素的表达.
- NSP12显著改变宿主mRNA的翻译效率,影响像NIK/NF-κB信号通路这样的通路.
结论:
- SARS-CoV-2 NSP12 劫持了宿主 eEF1A,以调节宿主 mRNA 翻译并抑制抗病毒反应.
- 这些发现提供了对病毒病原学的见解,并确定了COVID-19的潜在治疗点.
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