Integrated omics in Drosophila uncover a circadian kinome

Integrated omics in Drosophila uncover a circadian kinome
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果蝇的综合组学揭示了昼夜节律激酶组

DOI:
10.1038/s41467-020-16514-z
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发表时间:
2020
影响因子:
16.6
通讯作者:
Zhang L
Zhang L
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Wang C;Shui K;Ma S;Lin S;Zhang Y;Wen B;Deng W;Xu H;Hu H;Guo A;Xue Y;Zhang L

文献摘要

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地球上的大多数生物在行为和生理上表现出昼夜节律,这是由内源性时钟驱动的。磷酸化在生物钟计时中发挥着核心作用,但其如何影响明显的节律尚不清楚。在这里,我们使用果蝇头结合转录组和蛋白质组分析进行磷酸蛋白质组学。通过开发整合多组学数据的管道,我们确定了 789 个(约 17%)具有昼夜节律振荡的磷酸化位点。我们预测有 27 种潜在的昼夜节律激酶参与这些位点的磷酸化,其中包括 7 种之前已知在生物钟中发挥作用的激酶。我们筛选了其余 20 种激酶对昼夜节律的影响,并发现另外 3 种激酶参与调节运动节律。我们重新构建了一个包含 10 种昼夜节律激酶的信号网,并将 GASKET 确定为潜在的重要调节因子。总而言之,我们发现了一种昼夜节律激酶组,它可能塑造整个昼夜节律分子景观的时间模式。
Most organisms on the earth exhibit circadian rhythms in behavior and physiology, which are driven by endogenous clocks. Phosphorylation plays a central role in timing the clock, but how this contributes to overt rhythms is unclear. Here we conduct phosphoproteomics in conjunction with transcriptomic and proteomic profiling using fly heads. By developing a pipeline for integrating multi-omics data, we identify 789 (~17%) phosphorylation sites with circadian oscillations. We predict 27 potential circadian kinases to participate in phosphorylating these sites, including 7 previously known to function in the clock. We screen the remaining 20 kinases for effects on circadian rhythms and find an additional 3 to be involved in regulating locomotor rhythm. We re-construct a signal web that includes the 10 circadian kinases and identify GASKET as a potentially important regulator. Taken together, we uncover a circadian kinome that potentially shapes the temporal pattern of the entire circadian molecular landscapes.