miR-124Regulates the Phase ofDrosophilaCircadian Locomotor Behavior

Abstract

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 (Ϸ22 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.

The auxin‐inducible degradation system enables conditional PERIOD protein depletion in the nervous system of Drosophila melanogaster

“…A,B). Indeed, the oscillation of tagged PER in circadian neurons was similar with previous studies . Furthermore, circadian clocks have been shown to operate in many peripheral tissues, such as the Malpighian tubules .…”

Circadian regulation of microRNA-target chimeras in Drosophila

“…S5). This phenotype was also observed in miR-124 mutant 55, 56 . Our CLEAR-CLIP data suggest that miR-124 targets shaker (sh) and twenty-four (tyf) .…”

“…Decoding of the miRNA-mRNA interaction network is difficult because of incomplete complementary pairing between miRNAs and targets as well as context-dependent dynamics of the miRNA-target interactions. As a result, some miRNAs such as miR-124 and miR-959-964 have been shown to be involved in circadian rhythms but without known targets 29, 34, 35 . Thus, a global identification of circadian-related miRNA-target interactions will greatly improve our understanding of the role of miRNAs in circadian regulation.…”

Regulation of Circadian Behavior by Astroglial MicroRNAs inDrosophila

“…As each miRNA regulates many target RNAs, this strategy represents an efficient way to identify glial factors important for rhythmicity. miRNAs have been implicated in regulation of the molecular circadian clock or output pathways downstream of the clock (Cheng et al 2007;Yang et al 2008;Kadener et al 2009;Shende et al 2011;Luo and Sehgal 2012;Vodala et al 2012;Chen et al 2013;Zhang and Emery 2013;Chen and Rosbash 2016;Zhang et al 2016); however, there are no studies, to our knowledge, of glial miRNAs that regulate rhythmic behavior.…”