艾滋病毒Rev的调控取决于对拼接部位的识别
1Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139.
Cell
|December 1, 1989
概括
艾滋病毒Rev蛋白通过与拼接部位相互作用来调节未拼接RNA水平. 破坏拼接部位允许Rev蛋白将未拼接的RNA移动到细胞质中,这表明Rev解离了拼接因子.
科学领域:
- 分子生物学分子生物学
- 病毒学 病毒学
- 在RNA生物学,RNA生物学.
背景情况:
- 人类免疫缺陷病毒 (HIV) 的Rev蛋白对病毒复制至关重要,它调解从核到细胞质的未结合和部分结合的病毒RNA的输出.
- 调节RNA传输是基因表达的一个关键步骤,特别是在利用替代拼接的HIV等复杂病毒中.
- Rev反应元件 (RRE) 是一种特定的RNA序列,它与Rev蛋白结合,从而促进含有RRE的RNAs的核出口.
研究的目的:
- 研究拼接部位在Rev蛋白介导的调节未拼接RNA水平中的作用.
- 为了确定拼接位的完整性是否对于Rev蛋白功能在控制RNA局部化方面是必要的.
- 阐明Rev蛋白促进细胞质中未结合RNA的积累的机制.
主要方法:
- 使用一种含有Rev响应元素 (RRE) 的β-环球蛋白基因构造.
- 在β-环球蛋白前mRNA的5'和3'连接部位引入了突变.
- 评估了在Rev蛋白存在或不存在的情况下未拼接RNA的局部化,使用北方涂抹和亚细胞分离等技术.
主要成果:
- 野生类型的β-环球蛋白前mRNA具有完整的RRE并未受到Rev蛋白的调节.
- 在5'或3'拼接部位的突变使得β-环球蛋白前mRNARev响应.
- 这些突变未结合的RNAs在核中积累,直到Rev蛋白被引入,之后它们被发现在细胞质中.
结论:
- 艾滋病毒Rev蛋白调节未结合RNA水平的能力取决于结合部位的完整性.
- Rev蛋白介导调节可能涉及从前mRNA剪接组件的解离.
- 细胞拼接机器的拼接位点识别可能会在细胞核中保留未拼接的RNA,Rev蛋白促进它们的释放.
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