在SARS-CoV-2中识别Hammerhead变体的 ribozyme 序列
Getong Liu1,2, Hengyi Jiang1,2, Dongrong Chen1,2
1Shanghai Pudong Hospital, Fudan University Pudong Medical Center and Institutes of Biomedical Sciences, Shanghai Medical College, Key Laboratory of Medical Epigenetics and Metabolism, Fudan University, Shanghai 200032, China.
Nucleic acids research
|January 31, 2024
概括
研究人员在SARS-CoV-2基因组中发现了39种子头变异 ribozymes (CoV-HHRz). 这些 ribozymes 在各种变体中保存,并且可能在病毒RNA处理和复制中发挥作用.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 生物化学 生化学
背景情况:
- 由SARS-CoV-2病毒引起的COVID-19大流行需要对其基因组和生物机制有更深入的了解.
- 尽管进行了广泛的研究,但在SARS-CoV-2基因组中之前还没有发现任何 ribozymes.
研究的目的:
- 为了识别和描述SARS-CoV-2基因组内的新型 ribozyme 序列.
- 调查这些已识别的 ribozymes 的潜在 in vitro 和 in vivo 活性.
主要方法:
- 在SARS-CoV-2基因组中,生物信息分析以确定子头变异的 ribozyme 序列 (CoV-HHRz).
- 在体外生化测试以评估 ribozyme 分裂活性,包括pH和离子依赖性.
- 在SARS-CoV-2变种和其他冠状病毒中对Cov-HHRz保护的比较.
- 使用转录组数据,与已知的亚基因组RNA (sgRNA) 断点相关联的Cov-HHRz切割点.
主要成果:
- 在SARS-CoV-2变体中高度保存的39个头变体的 ribozyme 序列 (CoV-HHRz) 的鉴定.
- CoV-HHRz表现出典型的 ribozyme 特性,包括pH值和离子依赖裂变,在Mn2+ 存在时具有最佳活性.
- 四个Cov-HHRz的切割部位与SARS-CoV-2中表达的sgRNA的断点保持一致,这表明了潜在的体内功能.
- 这些核酶参与处理ORF7b,ORF10和ORF1ab nsp13的sgRNA,这对病毒包装和生命周期至关重要.
结论:
- 在SARS-CoV-2中发现的Cov-HHRz扩大了我们对病毒RNA处理机制的理解.
- 这些 ribozymes 在SARS-CoV-2 变体中保存,并显示出在 sgRNA 处理中体内活性的潜力.
- CoV-HHRz可能是针对SARS-CoV-2的抗病毒策略的新目标.
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