MiR-980 Is a Memory Suppressor MicroRNA that Regulates the Autism-Susceptibility Gene A2bp1

Cell Rep. 2016 Feb 23;14(7):1698-1709. doi: 10.1016/j.celrep.2016.01.040. Epub 2016 Feb 11.


MicroRNAs have been associated with many different biological functions, but little is known about their roles in conditioned behavior. We demonstrate that Drosophila miR-980 is a memory suppressor gene functioning in multiple regions of the adult brain. Memory acquisition and stability were both increased by miR-980 inhibition. Whole cell recordings and functional imaging experiments indicated that miR-980 regulates neuronal excitability. We identified the autism susceptibility gene, A2bp1, as an mRNA target for miR-980. A2bp1 levels varied inversely with miR-980 expression; memory performance was directly related to A2bp1 levels. In addition, A2bp1 knockdown reversed the memory gains produced by miR-980 inhibition, consistent with A2bp1 being a downstream target of miR-980 responsible for the memory phenotypes. Our results indicate that miR-980 represses A2bp1 expression to tune the excitable state of neurons, and the overall state of excitability translates to memory impairment or improvement.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Autism Spectrum Disorder / genetics
  • Autism Spectrum Disorder / metabolism
  • Autism Spectrum Disorder / pathology
  • Base Sequence
  • Brain / growth & development
  • Brain / metabolism*
  • Conditioning, Classical / physiology
  • Disease Models, Animal
  • Drosophila Proteins / antagonists & inhibitors
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / metabolism
  • Gene Expression Regulation, Developmental
  • Genetic Predisposition to Disease
  • Humans
  • Memory / physiology*
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Molecular Sequence Data
  • Olfactory Receptor Neurons / cytology
  • Olfactory Receptor Neurons / metabolism*
  • Protein Binding
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism
  • RNA-Binding Proteins / antagonists & inhibitors
  • RNA-Binding Proteins / genetics*
  • RNA-Binding Proteins / metabolism
  • Signal Transduction
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • Drosophila Proteins
  • GAL4 protein, Drosophila
  • MicroRNAs
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • Rbfox1 protein, Drosophila
  • Transcription Factors