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bioRxiv · 10.1101/399873

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

Leigh, W.·Liu, Z.·Nian, X.·Zhang, Y.
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Abstract

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-210KO) exhibit a dramatic phase advance of evening anticipatory behavior about 2 hours. However, circadian rhythms and molecular pacemaker function are intact in miR-210KO 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{Delta}miR-210) by CRISPR-Cas9 advances the evening phase as in miR-210KO. Indeed, miR-210 genetically interacts with Fas2. Moreover, Fas2 abundance is significantly increased in the optic lobe of miR-210KO and Fas2{Delta}miR-210. In addition, overexpression of Fas2 in the miR-210 expressing cells recapitulates the phase advance behavior phenotype of miR-210KO. Together, these results reveal a novel mechanism by which miR-210 regulates circadian locomotor behavior.\n\nAuthor 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-210s 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.

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Leigh, W., Liu, Z., Nian, X., Zhang, Y.. 2018-08-24. miR-210 controls the evening phase of circadian locomotor rhythms through repression of Fasciclin 2. https://doi.org/10.1101/399873

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