一个病毒泛末端RNA元素和宿主复合体定义了一个SARS-CoV-2 regulon
Debjit Khan1, Fulvia Terenzi1, GuanQun Liu2
1Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, OH, 44195, USA.
Nature communications
|June 9, 2023
概括
病毒SARS-CoV-2使用宿主蛋白质EPRS1,将特定的RNA元素 (SPEAR) 结合到其遗传物质上,从而促进病毒复制. 针对这种相互作用可以显著降低病毒载量,从而提供潜在的泛沙尔贝病毒疗法.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 在RNA生物学,RNA生物学.
背景情况:
- SARS-CoV-2 产生具有相同结尾的亚基因组RNA (sgRNA),这对于基因表达调节至关重要.
- 这些sgRNA终端和宿主病毒相互作用在基因表达中的作用仍然不完全理解.
研究的目的:
- 阐明宿主因子调节SARS-CoV-2sgRNA表达的机制.
- 确定控制SARS-CoV-2和相关病毒的新型治疗点.
主要方法:
- 在病毒3'-end.中识别特定RNA元素 (SPEAR).
- 研究谷氨基--tRNA合成酶 (EPRS1) 与SPEAR元素的结合.
- 评估SPEAR-EPRS1相互作用对病毒RNA翻译和框架转移的影响.
- 评估针对SPEAR元素的治疗策略.
主要成果:
- 在SARS-CoV-2 3'-ends中发现了SPEAR元素,该元素在宿主代理或病毒尖端蛋白诱导后与EPRS1结合.
- 证明ORF10的翻译对于SPEAR介导的sgRNA表达的诱导至关重要.
- 表明SPEAR元素增强了病毒编程的核糖体框架转移.
- 针对SPEAR的战略在实验模型中显著降低了SARS-CoV-2病毒标位.
结论:
- SARS-CoV-2 通过 SPEAR 元素劫持宿主蛋白 EPRS1,以增强病毒RNA 翻译和复制.
- 病毒通过选择宿主蛋白质功能来建立后转录的规律.
- 针对SPEAR-EPRS1相互作用是一个有前途的泛-sarbcoviral治疗策略.
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