一个依赖于平衡的逆转录病毒mRNA开关调节翻译重编码
Brian Houck-Loomis1, Michael A Durney, Carolina Salguero
1Department of Biochemistry and Molecular Biophysics, Howard Hughes Medical Institute, Columbia University, New York, New York 10032, USA.
Nature
|November 29, 2011
概括
逆转录病毒使用RNA重编码精确控制蛋白质水平. 鼠类白血病病毒RNA中的一个质子依赖开关调节了这一过程,保持了关键的Gag到Gag-Pol蛋白比率.
科学领域:
- 分子生物学分子生物学
- 病毒学 病毒学
- 结构生物学 结构生物学
背景情况:
- 复原病毒需要精确的Gag和Gag-Pol蛋白比率来组装.
- 通过核糖体框架转移或停止子读通的翻译重编实现了这种比率.
- 控制重新编码频率的机制仍然难以捉摸.
研究的目的:
- 阐明逆转录病毒转化重编码背后的机制.
- 为了确定cisRNA基因如何调节Gag与Gag-Pol蛋白质的比率.
- 为了研究小鼠白血病病毒重新编码的结构基础.
主要方法:
- 核磁共振 (NMR) 光谱法用于确定RNA结构.
- 对质子化依赖的形状开关的分析.
- RNA构成与体内蛋白质表达水平的相关性.
主要成果:
- 解决了小鼠白血病病毒重编码信号的NMR结构.
- 一个依赖于质子化的开关会诱导一个活跃的,读透的允许性结构.
- 这种活性构造在生理pH值下占~6%,与体内蛋白质比率相匹配.
- 该RNA利用化学机械合进行精确的读透频率控制.
结论:
- 在逆转录病毒中,一种新的基于平衡的机制控制着翻译重编码.
- 核突依赖的RNA形状变化是维持Gag/Gag-Pol比率的关键.
- 这种机制可能广泛适用于其他翻译重编码事件,包括移.
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