SARS-CoV-2的Nsp14通过准核帽结合复合体来抑制mRNA处理和核出口
Jun Katahira1, Tatsuya Ohmae1, Mayo Yasugi2
1Laboratory of Cellular Molecular Biology, Graduate School of Veterinary Sciences, Osaka Metropolitan University, 1-58 Rinku-Orai-kita, Izumisano, Osaka 598-8531, Japan.
Nucleic acids research
|June 1, 2023
概括
这就是SARS-CoV-2病毒.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 基因表达规范 基因表达规范
背景情况:
- 病毒破坏宿主基因表达以进行复制.
- 核出口的信使RNA (mRNA) 是一个常见的病毒目标.
- 严重急性呼吸道综合征冠状病毒2 (SARS-CoV-2) 抑制mRNA核出口.
研究的目的:
- 确定mRNA核出口的新型SARS-CoV-2抑制剂.
- 研究SARS-CoV-2阻断宿主基因表达的机制.
- 确定病毒蛋白Nsp14在mRNA加工和出口中的作用.
主要方法:
- 全基因组基因表达分析.
- 病毒蛋白Nsp14的突变分析.
- 毛细电泳质谱仪 (CE-MS) 用于代谢物检测.
- 核结复合体 (NCBC) 协会的分析.
主要成果:
- Nsp14被确定为一种新的mRNA核出口抑制剂.
- Nsp14导致聚A) +RNA的核积累和核斑点破坏.
- Nsp14诱导全球拼接和3'-end处理缺陷,特别是在基因素mRNA中.
- Nsp14的关氨酸-N7-甲基转移酶活性产生N7-甲基-GTP,损害NCBC功能.
- Nsp14抑制了mRNA盖结合和U1 snRNP和SLBP的招募.
结论:
- SARS-CoV-2 Nsp14 抑制了宿主mRNA的处理和出口.
- Nsp14的N7-甲基转移酶活性产生N7-甲基-GTP,影响NCBC功能.
- 这种机制代表了一种新的病毒策略,用于抑制宿主基因表达.
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