Preservation of ∼12-h ultradian rhythms of gene expression of mRNA and protein metabolism in the absence of canonical circadian clock.

Preservation of ∼12-h ultradian rhythms of gene expression of mRNA and protein metabolism in the absence of canonical circadian clock.
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DOI:
10.3389/fphys.2023.1195001
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发表时间:
2023
影响因子:
4
通讯作者:
--
中科院分区:
医学2区
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前言:从甲壳动物到哺乳动物,除了∼的24小时昼夜节律外,还存在着∼12小时的基因表达、代谢和行为的超常节律。关于∼12-h节律的起源和调节机制,提出了三个主要假说,即它们不是细胞自主的,受生物钟和环境信号的组合控制,它们是由两个反相的昼夜节律转录因子以细胞自主的方式调节的,或者它们是由一个细胞自主的∼12-h振荡器建立的。方法:为了区分这些可能性,我们对动物和缺乏典型生物钟的细胞的两个高时间分辨率转录组数据集进行了后期分析。结果:在BMAL1基因敲除小鼠的肝脏和果蝇S2细胞中,我们观察到在基因和蛋白质代谢的基本过程中丰富的∼基因表达的强健和普遍的12-h节律,这些节律与野生型小鼠的肝脏表现出很大的趋同性。生物信息学分析进一步预测,Elf1和ATF6B可能是转录因子,在苍蝇和小鼠中调节∼12-h基因表达的节律,而不依赖于生物钟。讨论:这些发现提供了额外的证据,支持进化上保守的12-h振荡器的存在,该振荡器控制着多种物种中蛋白质和∼代谢的基因表达的12-h节律。
Introduction: Besides the ∼24-h circadian rhythms, ∼12-h ultradian rhythms of gene expression, metabolism and behaviors exist in animals ranging from crustaceans to mammals. Three major hypotheses were proposed on the origin and mechanisms of regulation of ∼12-h rhythms, namely, that they are not cell-autonomous and controlled by a combination of the circadian clock and environmental cues, that they are regulated by two anti-phase circadian transcription factors in a cell autonomous manner, or that they are established by a cell-autonomous ∼12-h oscillator. Methods: To distinguish among these possibilities, we performed a post hoc analysis of two high temporal resolution transcriptome dataset in animals and cells lacking the canonical circadian clock. Results: In both the liver of BMAL1 knockout mice and Drosophila S2 cells, we observed robust and prevalent ∼12-h rhythms of gene expression enriched in fundamental processes of mRNA and protein metabolism that show large convergence with those identified in wild-type mice liver. Bioinformatics analysis further predicted ELF1 and ATF6B as putative transcription factors regulating the ∼12-h rhythms of gene expression independently of the circadian clock in both fly and mice. Discussion: These findings provide additional evidence to support the existence of an evolutionarily conserved 12-h oscillator that controls ∼12-h rhythms of gene expression of protein and mRNA metabolism in multiple species.
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