Zhang Yong, Lamba Pallavi, Guo Peiyi, Emery Patrick
Department of Neurobiology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, and Department of Biology, University of Nevada, Reno, Nevada 89557
Department of Neurobiology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, and.
J Neurosci. 2016 Feb 10;36(6):2007-13. doi: 10.1523/JNEUROSCI.3286-15.2016.
Animals use circadian rhythms to anticipate daily environmental changes. Circadian clocks have a profound effect on behavior. In Drosophila, for example, brain pacemaker neurons dictate that flies are mostly active at dawn and dusk. miRNAs are small, regulatory RNAs (≈22 nt) that play important roles in posttranscriptional regulation. Here, we identify miR-124 as an important regulator of Drosophila circadian locomotor rhythms. Under constant darkness, flies lacking miR-124 (miR-124(KO)) have a dramatically advanced circadian behavior phase. However, whereas a phase defect is usually caused by a change in the period of the circadian pacemaker, this is not the case in miR-124(KO) flies. Moreover, the phase of the circadian pacemaker in the clock neurons that control rhythmic locomotion is not altered either. Therefore, miR-124 modulates the output of circadian clock neurons rather than controlling their molecular pacemaker. Circadian phase is also advanced under temperature cycles, but a light/dark cycle partially corrects the defects in miR-124(KO) flies. Indeed, miR-124(KO) shows a normal evening phase under the latter conditions, but morning behavioral activity is suppressed. In summary, miR-124 controls diurnal activity and determines the phase of circadian locomotor behavior without affecting circadian pacemaker function. It thus provides a potent entry point to elucidate the mechanisms by which the phase of circadian behavior is determined.
In animals, molecular circadian clocks control the timing of behavioral activities to optimize them with the day/night cycle. This is critical for their fitness and survival. The mechanisms by which the phase of circadian behaviors is determined downstream of the molecular pacemakers are not yet well understood. Recent studies indicate that miRNAs are important regulators of circadian outputs. We found that miR-124 shapes diurnal behavioral activity and has a striking impact on the phase of circadian locomotor behavior. Surprisingly, the period and phase of the neural circadian pacemakers driving locomotor rhythms are unaffected. Therefore, miR-124 is a critical modulator of the circadian output pathways that control circadian behavioral rhythms.
动物利用昼夜节律来预测日常环境变化。昼夜节律钟对行为有深远影响。例如，在果蝇中，脑起搏器神经元决定果蝇大多在黎明和黄昏时活跃。微小RNA（miRNA）是小的调节性RNA（约22个核苷酸），在转录后调控中发挥重要作用。在这里，我们确定miR-124是果蝇昼夜运动节律的重要调节因子。在持续黑暗条件下，缺乏miR-124的果蝇（miR-124基因敲除果蝇）具有显著提前的昼夜行为相位。然而，虽然相位缺陷通常是由昼夜起搏器周期的变化引起的，但miR-124基因敲除果蝇并非如此。此外，控制节律性运动的时钟神经元中昼夜起搏器的相位也没有改变。因此，miR-124调节昼夜节律钟神经元的输出，而不是控制其分子起搏器。在温度循环下，昼夜相位也会提前，但光/暗循环部分纠正了miR-124基因敲除果蝇的缺陷。事实上，在后者条件下，miR-124基因敲除果蝇表现出正常的傍晚相位，但早晨的行为活动受到抑制。总之，miR-124控制昼夜活动，并决定昼夜运动行为的相位，而不影响昼夜起搏器功能。因此，它为阐明昼夜行为相位确定机制提供了一个有力的切入点。
在动物中，分子昼夜节律钟控制行为活动的时间，以使其与昼夜循环相优化。这对它们的适应性和生存至关重要。在分子起搏器下游确定昼夜行为相位的机制尚未完全了解。最近的研究表明，miRNA是昼夜节律输出的重要调节因子。我们发现miR-124塑造昼夜行为活动，并对昼夜运动行为的相位有显著影响。令人惊讶的是，驱动运动节律的神经昼夜起搏器的周期和相位不受影响。因此，miR-124是控制昼夜行为节律的昼夜节律输出途径的关键调节因子。
