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We describe a genome-wide microRNA (miRNA)-based screen to identify brain glial cell functions required for circadian behavior. To identify glial miRNAs that regulate circadian rhythmicity, we employed a collection of "miR-sponges" to inhibit miRNA function in a glia-specific manner. Our initial screen identified 20 glial miRNAs that regulate circadian behavior. We studied two miRNAs, miR-263b and miR-274, in detail and found that both function in adult astrocytes to regulate behavior. Astrocyte-specific inhibition of miR-263b or miR-274 in adults acutely impairs circadian locomotor activity rhythms with no effect on glial or clock neuronal cell viability. To identify potential RNA targets of miR-263b and miR-274, we screened 35 predicted miRNA targets, employing RNA interference-based approaches. Glial knockdown of two putative miR-274 targets, CG4328 and MESK2, resulted in significantly decreased rhythmicity. Homology of the miR-274 targets to mammalian counterparts suggests mechanisms that might be relevant for the glial regulation of rhythmicity.

Original publication

DOI

10.1534/genetics.117.300342

Type

Journal article

Journal

Genetics

Publication Date

03/2018

Volume

208

Pages

1195 - 1207

Keywords

astrocyte, circadian behavior, glial biology, microRNA, Animals, Astrocytes, Circadian Rhythm, Drosophila, Gene Knockout Techniques, Immunohistochemistry, Locomotion, MicroRNAs, Neuroglia, Organ Specificity