The orphan nuclear receptor RORα regulates circadian transcription of the mammalian core-clock Bmal1
The orphan nuclear receptor RORα regulates circadian transcription of the mammalian core-clock Bmal1
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DOI：
10.1038/nsmb925
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发表时间：
2005-05-01
影响因子：
16.8
通讯作者：
Takumi, T
中科院分区：
文献类型：
--
作者：
Akashi, M;Takumi, T
PAS（PER-ARNT-SIM）螺旋-环-螺旋转录因子BMAL 1（也称为MOP 3）是哺乳动物昼夜节律起搏器的重要组成部分。在这里，我们表明，视黄酸受体相关的孤儿受体ROR α（NR 1F 1）直接激活转录的Bmal 1通过两个保守的ROR α反应元件，所需的细胞自主转录振荡的Bmal 1 mRNA。ROR α在Bmal 1昼夜节律振荡的产生中的积极参与通过ROR α缺陷的蹒跚小鼠的行为分析来验证，所述小鼠显示异常的运动活动和不稳定的节律性。在培养的细胞中，内源性ROR α蛋白的丢失导致Bmal 1转录的昼夜节律减弱，进一步表明ROR α是细胞自主核心昼夜节律钟的功能组分。这些结果表明，ROR α的作用，以促进Bmal 1转录，从而保持一个强大的昼夜节律。
The PAS (PER-ARNT-SIM) helix-loop-helix transcription factor BMAL1 ( also known as MOP3) is an essential component of the circadian pacemaker in mammals. Here we show that the retinoic acid receptor - related orphan receptor ROR alpha (NR1F1) directly activates transcription of Bmal1 through two conserved ROR alpha response elements that are required for cell-autonomous transcriptional oscillation of Bmal1 mRNA. Positive involvement of ROR alpha in generation of the Bmal1 circadian oscillation was verified by behavioral analyses of ROR alpha-deficient staggerer mice that showed aberrant locomotor activity and unstable rhythmicity. In cultured cells, loss of endogenous ROR alpha protein resulted in a dampened circadian rhythm of Bmal1 transcription, further indicating that ROR alpha is a functional component of the cell-autonomous core circadian clock. These results indicate that ROR alpha acts to promote Bmal1 transcription, thereby maintaining a robust circadian rhythm.