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

Nat Commun. 2017 Mar 9:8:14707. doi: 10.1038/ncomms14707.


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.

MeSH terms

  • Animals
  • Cell Line
  • Circadian Clocks / genetics*
  • Circadian Rhythm / genetics*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / physiology
  • Gene Expression Regulation*
  • MicroRNAs / genetics*
  • Models, Genetic
  • Neurons / metabolism
  • Neurons / physiology*
  • Neuropeptides / metabolism
  • Sirtuin 2 / genetics
  • Sirtuin 2 / metabolism


  • Drosophila Proteins
  • MIRN92a microRNA, Drosophila
  • MicroRNAs
  • Neuropeptides
  • Sirtuin 2