The role of cell-autonomous circadian oscillation of Cry transcription in circadian rhythm generation
The role of cell-autonomous circadian oscillation of Cry transcription in circadian rhythm generation
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DOI：
10.1016/j.celrep.2022.110703
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发表时间：
2022-04-19
期刊：
影响因子：
8.8
通讯作者：
Akashi, Makoto
中科院分区：
文献类型：
--
作者：
Matsumura, Ritsuko;Yoshimi, Kazuto;Akashi, Makoto
哺乳动物生物钟的当前模型将Cry和Per转录的细胞自主和负反馈驱动的生物钟振荡描述为核心生物钟发生器。然而，这种振荡对昼夜节律产生的实际贡献仍然不确定。在这里，我们进行有针对性的破坏顺式元件不可或缺的细胞自主的Cry振荡。缺乏明显的细胞自主Cry振荡的小鼠在运动活动中显示出稳健的昼夜节律。此外，在没有明显的Cry振荡的情况下，组织自主的昼夜节律是稳健的。出乎意料的是，虽然没有明显的Cry振荡导致细胞自主水平的Per振荡严重衰减，但Per 2积累的昼夜节律仍然稳健。作为解释这一违反直觉的结果的机制，Per2半衰期显示了独立于Cry和Per振荡的细胞自主昼夜节律。因此，即使在没有明显的Cry和Per振荡的情况下，细胞自主的昼夜节律钟也可以保持部分功能，因为Per2降解中的昼夜节律振荡。
The current model of the mammalian circadian clock describes cell-autonomous and negative feedback driven circadian oscillation of Cry and Per transcription as the core circadian rhythm generator. However, the actual contribution of this oscillation to circadian rhythm generation remains undefined. Here we perform targeted disruption of cis elements indispensable for cell-autonomous Cry oscillation. Mice lacking overt cell autonomous Cry oscillation show robust circadian rhythms in locomotor activity. In addition, tissue -autonomous circadian rhythms are robust in the absence of overt Cry oscillation. Unexpectedly, although the absence of overt Cry oscillation leads to severe attenuation of Per oscillation at the cell-autonomous level, circadian rhythms in Per2 accumulation remain robust. As a mechanism to explain this counterintuitive result, Per2 half-life shows cell-autonomous circadian rhythms independent of Cry and Per oscillation. The cell autonomous circadian clock may therefore remain partially functional even in the absence of overt Cry and Per oscillation because of circadian oscillation in Per2 degradation.