通过病毒挖矿发现功能性无因子内部核糖体进入站点样结构
Subash Chapagain1,2, Nicolas Salcedo-Porras1,2, Amir Abdolahzadeh1,2
1Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada.
PLoS pathogens
|June 26, 2025
概括
研究人员在病毒基因组中发现了新的RNA结构,这些结构劫持了宿主核糖体以合成蛋白质. 这些内部核糖体进入点 (IRES) 为病毒进化和翻译机制提供了新的见解.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 生物信息学是一种生物信息学.
背景情况:
- 病毒依赖宿主核糖体进行蛋白质合成.
- 狄基斯特病毒跨基因区域内部核糖体进入点 (IGR-IRESs) 使用独特的三重伪结结构从非AUG编码器开始翻译.
- 这些IRES机制的进化起源仍然是未知的.
研究的目的:
- 研究跨RNA病毒组的IRES的多样性和功能.
- 为了确定新的IRES样RNA结构及其起源.
- 了解利用基于RNA的翻译机制的病毒策略.
主要方法:
- 利用生物信息学管道与RNA共变性模型来搜索RNA病毒体中的IRES类结构.
- 使用双光透镜图书馆报告员屏幕来测试IRES功能.
- 进行了体外和体内测试,以确认核糖体结合和内部核糖体进入活性.
主要成果:
- 鉴定了超过4,700个类似迪克斯特罗的基因组,其中约32%含有假定的IRES结构.
- 发现了具有多个IRES和嵌入在开放阅读框架 (ORF) 中的IRES的新型病毒基因组安排.
- 证实预测的IRES与核糖体结合并调解内部核糖体进入活动,包括单基斯特基因组的ORF内的功能性内部IRES.
- 在非dicistrovirus家族 (Tombusviridae,Narnaviridae) 中发现了与IRES类似的结构,这些结构结合于核糖体,并可以指导内部核糖体的进入.
结论:
- 这项研究为绘制无因子IRES机制的起源提供了一个全面的框架.
- 揭示了利用基于RNA的翻译机制的多种病毒策略.
- 突出了IRES元素的流行和功能意义,超出了dicistroviruses.
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