title: MicroRNA-92a is a circadian modulator of neuronal excitability in Drosophila.
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.
authors.affiliation: Department of Biology, Howard Hughes Medical Institute and National Center for Behavioral Genomics, Brandeis University, Waltham, Massachusetts 02454, USA.
authors.forename: Xiao
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Biology, Howard Hughes Medical Institute and National Center for Behavioral Genomics, Brandeis University, Waltham, Massachusetts 02454, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Rosbash
mesh_terms: D000818:Animals; D002460:Cell Line; D057906:Circadian Clocks / Q000235:genetics*; D002940:Circadian Rhythm / Q000235:genetics*; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000502:physiology; D005786:Gene Expression Regulation; D035683:MicroRNAs / Q000235:genetics*; D008957:Models, Genetic; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism; D056565:Sirtuin 2 / Q000235:genetics / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; C000629244:MIRN92a microRNA, Drosophila; D035683:MicroRNAs; D009479:Neuropeptides; D056565:Sirtuin 2