Emerging roles for microRNA in the regulation of Drosophila circadian clock

Xue, Yongbo; Zhang, Yong

doi:10.1186/s12868-018-0401-8

Cited by 54 publications

(57 citation statements)

References 67 publications

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“…Post-transcriptional regulation by miRNA has been implicated in a broad range of processes, including the circadian system (Xue & Zhang 2018). Recent studies in plants revealed that miRNAs are also involved in the photoperiodic timing of flowering (Jung et al 2007;L.…”

Section: Introductionmentioning

confidence: 99%

Photoperiod-dependent expression of MicroRNA in Drosophila

Pegoraro

Tauber

2018

Preprint

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Like many other insects in temperate regions, Drosophila melanogaster exploits the photoperiod shortening that occurs during the autumn as an important cue to trigger a seasonal response. Flies survives the winter by entering a state of reproductive arrest (diapause), which drives relocation of resources from reproduction to survival. Here, we profiled the expression of microRNA (miRNA) in long and short photoperiods, and identified seven differentially expressed miRNAs (dme-mir-2b, dme-mir-11, dme-mir-34, dme-mir-274, dme-mir-184, dme-mir-184* and dme-mir-285). Misexpression of dme-mir-2b, dmemir-184 and dme-mir-274 in pigment-dispersing factor-expressing neurons largely disrupted the normal photoperiodic response, suggesting that these miRNAs play functional roles in photoperiodic timing. We also analyzed the targets of photoperiodic miRNA by both computational predication and by Argonaute-1mediated immunoprecipitation of long-and short-day RNA samples. Together with global transcriptome profiling, our results expand existing data on other Drosophila species, identifying genes and pathways that are differentially regulated in different photoperiods and reproductive status. Our data suggest that post-transcriptional regulation by miRNA is an important facet of photoperiodic timing.

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Section: Introductionmentioning

confidence: 99%

Photoperiod-dependent expression of MicroRNA in Drosophila

Pegoraro

Tauber

2018

Preprint

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“…Emerging roles of miRNA in the control of different aspects of circadian rhythms have been recently uncovered [33]. Here, we screen Drosophila miRNA mutants and demonstrate that miR-210 is critical for circadian locomotor rhythms.…”

Section: Discussionmentioning

confidence: 98%

“…miRNAs are small non-coding RNAs, which repress target gene expression through mRNA degradation and/or translation inhibition, thus play crucial roles in posttranscriptional regulation [31]. Recent studies have uncovered functions of the miRNA biogenesis pathway and specific miRNAs in the regulation of different aspects of animal circadian rhythms [30,[32][33][34]. For instance, mouse miR-132/212 modulates the seasonal adaptation and circadian entrainment to day length [35].…”

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confidence: 99%

miR-210 controls the evening phase of circadian locomotor rhythms through repression of Fasciclin 2

Leigh

Liu

Nian

et al. 2018

Preprint

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Circadian clocks control the timing of animal behavior rhythms to anticipate daily environmental changes. Fruit flies gradually increase their activity and reach a peak of activity around dawn and dusk. microRNAs are small non-coding RNAs that play important roles in post-transcriptional regulation. Here we identify Drosophila miR-210 as a critical regulator of circadian rhythms. Under light-dark conditions, flies lacking miR-210 (miR-210 KO ) exhibit a dramatic phase advance of evening anticipatory behavior about 2 hours. However, circadian rhythms and molecular pacemaker function are intact in miR-210 KO flies under constant darkness. Furthermore, we identify that miR-210 determines the evening phase of activity through repression of the cell adhesion molecule Fasciclin 2 (Fas2). Ablation of the miR-210 binding site within the 3' UTR of Fas2 (Fas2 ΔmiR-210 ) by CRISPR-Cas9 advances the evening phase as in miR-210 KO .Indeed, miR-210 genetically interacts with Fas2. Moreover, Fas2 abundance is significantly increased in the optic lobe of miR-210 . In addition, overexpression of Fas2 in the miR-210 expressing cells recapitulates the phase advance behavior phenotype of miR-210 KO . Together, these results reveal a novel mechanism by which miR-210 regulates circadian locomotor behavior. Author summaryCircadian clocks control the timing of animal physiology. Drosophila has been a powerful model in understanding the mechanisms of circadian regulation. Fruit flies anticipate daily environmental changes and exhibit two peaks of locomotor activity around dawn and dusk. Here we identify miR-210 as a critical regulator of evening anticipatory behavior. Depletion of miR-210 in flies advances evening anticipation. Futhermore, we identify the cell adhesion molecular Fas2 as miR-210's target in circadian regulation.Fas2 abundance is increased in fly brain lacking of miR-210. Using CRISPR-Cas9 genome editing method, we deleted the miR-210 binding site on 3' untranslated region of Fas2 and observed similar phenotype as miR-210 mutants. Altogether, our results indicate a novel mechanism of miR-210 in regulation of circadian anticipatory behavior through inhibition of Fas2. IntroductionThe circadian locomotor rhythms of flies are generated by a neuronal network, which consists of ~150 brain circadian neurons expressing core pacemaker genes [1][2][3][4]. These neurons can be further divided into 7 clusters based on their cell localization and neurotransmitters they express [4]. There are 3 groups of dorsal neurons (DN1, DN2, and DN3), 2 groups of ventral-lateral neurons (large and small LNv), dorsal lateral neurons (LNd), and lateral posterior neurons (LPN) [4]. The large LNvs (lLNvs) and 4 small LNvs (sLNvs) express the neuropeptide Pigment Dispersing Factor (PDF), while the 5 th sLNv is PDF negative. Under regular light-dark (LD) conditions, flies exhibit a bimodal pattern of locomotor rhythms, peaking around dawn and dusk, which are termed morning peak and evening peak, respectively. According to the dual-oscillator model, sep...

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“…The significance of post-transcriptional regulation in circadian rhythms has been demonstrated by monitoring the core clock gene expression 15, 52 and screening miRNAs involved in rhythmic behavior 44, 47–49, 53–58 . However, elucidation of the underlying molecular mechanism is impeded because only a few of the predicted miRNA-mRNA interactions have been verified.…”

Section: Discussionmentioning

confidence: 99%

“…Disruption of the miRNA biogenesis pathway considerably weakens the rhythm in locomotor activity 26 . Although the rhythmically expressed miRNAs have been identified 27–29 , only a limited set of miRNA-target pairs have been verified to affect circadian rhythms 26, 30–33 . 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.…”

Section: Introductionmentioning

confidence: 99%

Circadian regulation of microRNA-target chimeras in Drosophila

Xia

et al. 2019

Preprint

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41MicroRNA is critical coordinator to circadian regulation by silencing gene 42 expression. Although many circadian related miRNAs and some of its target are 43 known, the global functional miRNA-mRNA interaction networks remain poorly 44 understand which is hindered by imperfect base-pairing between miRNA and target 45 mRNA. In this study, we used CLEAR (Covalent Ligation of Endogenous 46Argonaute-bound RNAs) -CLIP (Cross-Linking and Immuno-Precipitation) to explore 47 the regulatory functions of miRNAs in the circadian system by comparing the 48 miRNA-mRNA interactions between the Drosophila wild-type strain w 1118 and the Clk 49 mutant Clk jrk . We unambiguously identified thousands of miRNA-mRNA interactions 50 from CLEAR-CLIP data set at unprecedented depth in vivo for the first time. Among 51 them, about 300 miRNA-mRNA interactions were involved in the regulation of 52 circadian, in which miRNAs targeting core clock genes pdp1, tim and vri presented 53 distinct changes in response to Clk jrk . Particularly, the mir-375-timeless interaction 54 from CLER-CLIP shows important effects on circadian, this functional event occurred 55 in the l-LNv neurons. Overexpression of mir-375 in tim neurons caused decreases in 56 TIM content resulting in arrhythmicity of daily locomotion and changes of sleep. This 57 present work provides a global view of miRNA targeting in the circadian rhythm. 58 59 Keywords: CLEAR-CLIP, miRNAs, circadian rhythm, sleep, miR-375 60 61 62 In animals, the intrinsic circadian clock regulates daily rhythms in physiology and 64 behavior, which are entrained by environmental stimuli such as light and 65 temperature 1, 2 . This robust timing system maintains rhythmic oscillation even under 66 constant darkness conditions in the fruit fly Drosophila melanogaster. 67 Sleep is one of the established circadian behavior, which is highly associated with 68 health status 3 . Sleep in Drosophila has been well characterized by certain parameters 69 such as total sleep, sleep bout duration and sleep bout number 4-6 . Throughout the daily 70 sleep-wake cycle, the flies exhibit two peaks of activity -one before lights on and one 71 before lights off. Genetic dissection in Drosophila indicates that sleep is regulated by 72 the circadian clock. The mutations of the core clock genes result in abnormal sleep 7, 8 , 73 while the neuropeptide pigment dispersing factor (PDF)-expressing peptidergic clock 74 neurons regulate arousal as well as sleep stability 9 . 75 The Drosophila rhythmic behavior is maintained by a central clock network in 76 the brain, which is consisted of ~150 circadian neurons 10 . These clock neurons 77 include ventral lateral neurons (LNvs) (I-LNvs, s-LNvs, and 5 th s-LNvs), dorsal 78 lateral neurons (LNds), lateral posterior neurons (LPN) and dorsal neurons (DN1, 79 DN2, and DN3), classified based on anatomical locations and varied expression of 80 core clock genes 10-13 . Among them, the PDF-positive neurons (I-LNvs and s-LNvs) 81 are essential for normal circadian activity and daily sleep. ...

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Emerging roles for microRNA in the regulation of Drosophila circadian clock

Cited by 54 publications

References 67 publications

Photoperiod-dependent expression of MicroRNA in Drosophila

Photoperiod-dependent expression of MicroRNA in Drosophila

miR-210 controls the evening phase of circadian locomotor rhythms through repression of Fasciclin 2

Circadian regulation of microRNA-target chimeras in Drosophila

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