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一个全基因组RNAi屏幕用于人类细胞中昼夜时钟的修饰者

Eric E Zhang¹, Andrew C Liu, Tsuyoshi Hirota

¹Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121, USA.

|September 22, 2009

概括

这项研究使用全基因组屏幕来识别新的时钟基因. 研究结果显示,昼夜时钟与必不可少的细胞功能 (如胰岛素信号传递和细胞周期调节) 相互关联.

科学领域:

分子生物学分子生物学
遗传学是一个遗传学.
时间生物学时间生物学

背景情况:

几十年的研究已经确定了关键的时钟基因和控制昼夜振荡器功能的生化反循环.
了解调节昼夜节律的完整基因网络对于理解细胞平衡至关重要.

研究的目的:

确定新的时钟基因和昼夜振荡器功能的修饰剂.
探索由昼夜节律调节影响的更广泛的细胞通路.

主要方法:

在人类细胞钟模型中进行了全基因组小干扰RNA (siRNA) 屏幕.
通过二次选验证了候选基因,并描述了它们的剂量依赖性影响.
进行了蛋白质相互作用网络和通路分析.

主要成果:

确定了近1000个基因,这些基因的淘汰减少了昼夜节律的幅度.
数百个影响周期长度或扩展幅度的基因被发现并得到证实.
确定了钟基因产物与胰岛素信号,刺信号,细胞循环和叶酸代谢途径之间的显著关联.

结论:

昼夜时钟与各种细胞功能密切相关,包括新陈代谢和细胞周期调节.
确定了修改昼夜振荡器功能的新型基因和途径,扩大了我们对时间生物学的理解.

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