通过IRES介导的HCV转化启动路径
Geoff A Otto1, Joseph D Puglisi
1Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Cell
|October 28, 2004
概括
肝炎C病毒 (HCV) 内部核糖体进入部位 (IRES) 使用独特的途径启动蛋白质合成,与标准细胞方法不同. 这一途径涉及病毒mRNA的序列复杂组合,对于病毒复制至关重要.
科学领域:
- 分子生物学分子生物学
- 病毒学 病毒学
- 生物化学 生物化学
背景情况:
- 规范性真核体翻译启动涉及多个真核体启动因子 (eIF) 和一个5'帽结构.
- 型肝炎病毒 (HCV) 使用内部核糖体进入部位 (IRES) 来启动独立于帽子的翻译.
- 了解HCVIRES介导翻译的精确机制对于开发抗病毒疗法至关重要.
研究的目的:
- 阐明由HCVIRES介导的翻译启动复合组合的顺序路径.
- 为了区分HCVIRES启动机制与正规的真核细胞转化.
- 调查高效HCVIRES功能的结构要求.
主要方法:
- 生物化学试验用于研究核糖体子单元和启动因子之间的复杂形成.
- 分析HCVIRESRNA结构及其在翻译启动中的作用.
- 在翻译启动过程中形成的中间复合物的表征.
主要成果:
- 型冠状病毒IRES形成了一个二元复合体,与40S核糖体子单元独立于eIFs.
- 一个类似48S的复合体在AUG编码子上与eIF3和三元复合体组合在一起.
- 80S核糖体的形成是一个依赖于GTP的速度限制步骤,取决于保存的IRES结构.
结论:
- 已经提出了HCVIRES介导的翻译启动的修订模型.
- 在HCV IRES中,用于翻译启动复杂组合的不同顺序路径.
- 保持HCV IRES结构对于高效的翻译启动至关重要.
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