冷诱导型RNA结合蛋白调节昼夜基因表达的转录后
Jörg Morf1, Guillaume Rey, Kim Schneider
1Department of Molecular Biology, University of Geneva, and National Centre of Competence in Research, Frontiers in Genetics, 30 Quai Ernest Ansermet, CH-1211 Geneva, Switzerland.
概括
模拟的体温周期调节冷诱导RNA结合蛋白 (CIRP) 的表达. 通过控制哺乳动物细胞中的CLOCK蛋白水平,CIRP对于稳健的昼夜基因表达至关重要.
科学领域:
- 分子生物学分子生物学
- 时间生物学 时间生物学
- 遗传学 是一个遗传学.
背景情况:
- 哺乳动物的日间基因表达受上神核主心脏起器和局部振荡器的影响.
- 特定蛋白质在调节昼夜节律中的作用需要进一步阐明.
研究的目的:
- 研究冷诱导性RNA结合蛋白 (CIRP) 在调节昼夜基因表达中的作用.
- 确定CIRP影响昼夜节律的分子机制.
主要方法:
- 模拟的体温周期被用来控制培养纤维细胞中的基因表达.
- 功能丧失实验评估了CIRP对昼夜基因表达的必要性.
- 基于生物素 - 链条维丁的交叉链接和免疫沉 (CLIP) 确定了与CIRP结合的RNA.
- 西方斑点和子宫外表达研究分析了CLOCK蛋白水平和功能.
主要成果:
- 模拟的体温周期,而不是外围振荡器,驱动了纤维细胞中的节奏CIRP表达.
- CIRP功能丧失损害了高幅度昼夜基因表达.
- CLIP确定了编码昼夜振荡器蛋白质的转录,包括CLOCK,由CIRP结合.
- 消耗CIRP显著减少了CLOCK积累,而它的异位表达恢复了昼夜基因表达.
结论:
- CIRP是昼夜基因表达幅度的关键调节者.
- 通过调节钟表表达式,CIRP赋予昼夜振荡器的稳定性.
- CIRP在温度周期的下游和CLOCK的上游作用,以保持昼夜节律.
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