MicroRNA-92a is a circadian modulator of neuronal excitability in Drosophila

Xiao Chen and Michael Rosbash ()
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Xiao Chen: Howard Hughes Medical Institute and National Center for Behavioral Genomics, Brandeis University
Michael Rosbash: Howard Hughes Medical Institute and National Center for Behavioral Genomics, Brandeis University

Nature Communications, 2017, vol. 8, issue 1, 1-11

Abstract: Abstract Many biological and behavioural processes of animals are governed by an endogenous circadian clock, which is dependent on transcriptional regulation. Here we address post-transcriptional regulation and the role of miRNAs in Drosophila circadian rhythms. At least six miRNAs show cycling expression levels within the pigment dispersing factor (PDF) cell-pacemaker neurons; only mir-92a peaks during the night. In vivo calcium monitoring, dynamics of PDF projections, ArcLight, GCaMP6 imaging and sleep assays indicate that mir-92a suppresses neuronal excitability. In addition, mir-92a levels within PDF cells respond to light pulses and also affect the phase shift response. Translating ribosome affinity purification (TRAP) and in vitro luciferase reporter assay indicate that mir-92a suppresses expression of sirt2, which is homologous to human sir2 and sirt3. sirt2 RNAi also phenocopies mir-92a overexpression. These experiments indicate that sirt2 is a functional mir-92a target and that mir-92a modulates PDF neuronal excitability via suppressing SIRT2 levels in a rhythmic manner.

Date: 2017
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DOI: 10.1038/ncomms14707

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