对HIV-1RNA命运的转录起点控制的结构基础
Joshua D Brown1, Siarhei Kharytonchyk2, Issac Chaudry1
1Howard Hughes Medical Institute and Department of Chemistry and Biochemistry, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, USA.
艾滋病毒-1RNA封顶上的5'-瓜诺辛数量决定了它的命运. 一个单一的瓜诺辛 (Cap1G) 形成了一个封闭盖的结构,而两个或三个瓜诺辛 (Cap2G/Cap3G) 暴露它进行翻译.
科学领域:
- 分子生物学
- 病毒学
- 结构生物学
背景情况:
- 艾滋病毒-1 基因表达涉及异质的 5'- caped RNA.
- 这些RNA在5'- guanosines (Cap1G,Cap2G,Cap3G) 的数量上有所不同.
- 5'-瓜诺辛的数量影响RNA命运:基因组包装或mRNA翻译.
研究的目的:
- 研究5'-瓜诺辛的数量如何影响HIV-1领导RNA的结构和命运.
- 阐明差异性RNA处理的结构机制.
主要方法:
- 用编辑的核磁共振 (NMR) 光谱.
- 对被封闭的HIV-1领导RNA进行结构探测.
主要成果:
- Cap1G转录采用二维的多毛结构,隔离帽子并抑制翻译启动因子4E结合.
- Cap2G和Cap3G的转录采用了暴露的帽子和拼接供体残留物的替代结构.
- 结构改造,涉及G-C基对的能量成本,将Cap1G与Cap2G/Cap3G结构区分开来.
结论:
- 5'- 瓜诺辛的数量显著改变了HIV-1的RNA结构.
- 结构变化决定了RNA的命运,影响了基因组包装与mRNA的翻译.
- 一个单一的5'-瓜诺辛修饰驱动大型病毒RNA转录中的功能分歧.
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