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全球控制替代分离的多价值hNNP组件的哺乳动物监管扩展
Serge Gueroussov1, Robert J Weatheritt2, Dave O'Hanlon3
1Donnelly Centre, University of Toronto, Toronto, ON, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
Cell
|July 15, 2017
概括
哺乳动物进化表明,替代拼接 (AS) 对RNA结合蛋白中的内在无序区域 (IDR) 产生影响. 这种AS控制蛋白质组合的形成,调节基因拼接并扩大细胞调节能力.
科学领域:
- 进化生物学
- 分子生物学
- 遗传学
背景情况:
- 在脊椎动物进化过程中,替代拼接 (AS) 模式迅速分离.
- 大多数物种和谱系特异性拼接事件的功能在很大程度上是未知的.
- 内在无序区域 (IDR) 对蛋白质的功能和调节至关重要.
研究的目的:
- 研究哺乳动物特异性AS事件的功能意义.
- 阐明AS在蛋白质相互作用和基因调节中的作用.
- 了解哺乳动物细胞中的调节机制的进化扩张.
主要方法:
- 对哺乳动物基因组的替代拼接模式的分析.
- 特定物种的AS事件的识别
- 对RNA-蛋白相互作用和复合物形成的研究.
- 关于AS对蛋白质组合和拼接调节的影响的功能研究.
主要成果:
- 哺乳动物特异性AS事件在编码内在无序区域 (IDR) 的蛋白质区域中得到丰富.
- 这些事件影响RNA结合蛋白家族 (hnRNP A和D) 并涉及糖氨酸/ 氨酸重复.
- 差异性外显子包括控制氨酸依赖的多价值 hnRNP 组件.
- 规则要求异常,长距离的哺乳动物特异性RNA复合体.
结论:
- 在 hnRNP 之间,AS 控制 IDR 介导的相互作用是关键的拼接调节机制.
- 这种机制扩大了哺乳动物细胞的调节能力.
- 在AS的进化变化有助于新的调节功能和潜在的人类疾病.
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