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与高度保守和超保守的DNA元素相关的SR基因的非生产性拼接
Liana F Lareau1, Maki Inada, Richard E Green
1Department of Molecular and Cell Biology and, University of California, Berkeley, California 94720, USA.
Nature
|March 16, 2007
概括
基因内的超保存元素,特别是SR拼接调节器中的超保存元素,被替代地拼接到.
科学领域:
- 基因组学就是基因组学.
- 分子生物学分子生物学
- 在RNA生物学,RNA生物学.
背景情况:
- 超保存元素 (UCE) 是人类和小鼠基因组之间共享的高度保存的序列.
- 虽然基因上游的UCE可以充当增强剂,但它们在基因中的作用,特别是在替代拼接的前基因中,仍然不清楚.
- 在RNA结合蛋白基因中,UCEs重叠的替代拼接外因子的功能在很大程度上是未知的.
研究的目的:
- 为了研究位于SR家族拼接调节器的替代拼接外子内部的超保守元素的功能.
- 通过替代拼接来确定这些保存区域是否在基因调节中发挥作用.
主要方法:
- 对人类SR蛋白基因中的替代拼接模式的分析.
- 在替代拼接的外子和内子中识别超保守的元素.
- 研究RNA监测途径,特别是无意义介导的mRNA衰变 (NMD).
- 在小鼠 ортолог的拼接模式的比较分析.
主要成果:
- 所有人类SR家族的拼接调节器都含有替代拼接的超保守元素.
- 这些元素以"毒盒外子"的形式与过早停止的子或作为替代3'未翻译区域内子结合在一起.
- 这些替代拼接事件触发了无意中介的mRNA衰变,导致mRNA降解.
- 类似的非生产性拼接模式在小鼠SR蛋白质ortologues中也被观察到.
- 与保存区域相关的非生产性拼接似乎在不同的SR基因中独立演变.
结论:
- 涉及超保存元素的非生产性替代拼接是整个SR蛋白家族的保存调节机制.
- 这种机制针对SR蛋白信使RNA通过无意义介导的mRNA衰变降解.
- 这种监管策略的独立演变表明拼接因素很容易采用它.
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