Reference - Detail
|Author||Guven-Ozkan T, Busto GU, Schutte SS, Cervantes-Sandoval I, O'Dowd DK, Davis RL.|
|Title||MiR-980 Is a Memory Suppressor MicroRNA that Regulates the Autism-Susceptibility Gene A2bp1.|
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.
|MeSH||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|
|WOS Category||CELL BIOLOGY|