全基因组的CRISPR屏幕识别非正规翻译因子eIF2A作为SARS-CoV-2编程-1核糖体框架转移的增强剂
Lian-Huan Wei1, Yu Sun1, Junjie U Guo1
1Department of Neuroscience, Yale University School of Medicine, New Haven, CT 06520, USA.
Cell reports
|August 15, 2023
概括
这项研究确定了真核转化启动因子2A (eIF2A) 作为一种增强SARS-CoV-2编程-1核糖体框架转移的宿主因子. 失去eIF2A减少了病毒复制,突出显示了它在冠状病毒转化中的作用.
科学领域:
- 分子生物学分子生物学
- 病毒学 病毒学
- 遗传学 遗传学 是一个
背景情况:
- 阳性链RNA病毒,包括冠状病毒,利用编程的-1核糖体框架转移 (-1PRF) 来进行多基RNA转化.
- 调节病毒-1PRF的宿主因素在很大程度上是未知的.
研究的目的:
- 使用全基因组屏幕识别调节SARS-CoV-2 -1 PRF的宿主因素.
- 调查已识别的因素在病毒复制和翻译中的特定作用.
主要方法:
- 全基因组的CRISPR-Cas9淘汰屏幕用于识别宿主因素.
- 试验评估宿主因素对SARS-CoV-2的直接影响 -1 PRF.
- 测量具有改变宿主因子水平的细胞中SARS-CoV-2复制的结果.
- 全转录组分析以确定RNA结合偏好.
主要成果:
- 识别了抑制或增强SARS-CoV-2的宿主因素.
- 发现真核细胞翻译启动因子2A (eIF2A) 能够独立于翻译启动,特别增强-1 PRF.
- 失去eIF2A显著减少了SARS-CoV-2的复制.
- eIF2A优先结合富含CG的RNA基因,包括靠近SARS-CoV-2框架转移刺激元件 (FSE) 和核糖体的区域.
结论:
- eIF2A在增强SARS-CoV-2 -1 PRF中发挥着至关重要的作用.
- eIF2A调节病毒RNA翻译独立于其在启动中的正规作用.
- 准eIF2A可能是抑制SARS-CoV-2复制的潜在策略.
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