title: MiR-980 Is a Memory Suppressor MicroRNA that Regulates the Autism-Susceptibility Gene A2bp1.
abstract: 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.
authors.affiliation: Department of Neuroscience, The Scripps Research Institute Florida, Jupiter, FL 33458, USA.
authors.forename: Tugba
authors.initials: T
authors.lastname: Guven-Ozkan
authors.affiliation: Department of Neuroscience, The Scripps Research Institute Florida, Jupiter, FL 33458, USA.
authors.forename: Germain U
authors.initials: GU
authors.lastname: Busto
authors.affiliation: Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA; Department of Anatomy and Neurobiology, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Soleil S
authors.initials: SS
authors.lastname: Schutte
authors.affiliation: Department of Neuroscience, The Scripps Research Institute Florida, Jupiter, FL 33458, USA.
authors.forename: Isaac
authors.initials: I
authors.lastname: Cervantes-Sandoval
authors.affiliation: Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697, USA; Department of Anatomy and Neurobiology, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Diane K
authors.initials: DK
authors.lastname: O'Dowd
authors.affiliation: Department of Neuroscience, The Scripps Research Institute Florida, Jupiter, FL 33458, USA. Electronic address: rdavis@scripps.edu.
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Davis
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000067877:Autism Spectrum Disorder / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D001483:Base Sequence; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D003214:Conditioning, Classical / Q000502:physiology; D004195:Disease Models, Animal; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D020022:Genetic Predisposition to Disease; D006801:Humans; D008568:Memory / Q000502:physiology*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D018034:Olfactory Receptor Neurons / Q000166:cytology / Q000378:metabolism*; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; C557617:GAL4 protein, Drosophila; D035683:MicroRNAs; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C500367:Rbfox1 protein, Drosophila; D014157:Transcription Factors