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

Tugba Guven-Ozkan; Germain U Busto; Soleil S Schutte; Isaac Cervantes-Sandoval; Diane K O'Dowd; Ronald L Davis

doi:10.1016/j.celrep.2016.01.040

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.

Authors

Tugba Guven-Ozkan¹, Germain U Busto¹, Soleil S Schutte², Isaac Cervantes-Sandoval¹, Diane K O'Dowd², Ronald L Davis³

Affiliations

¹ Department of Neuroscience, The Scripps Research Institute Florida, Jupiter, FL 33458, USA.
² 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.
³ Department of Neuroscience, The Scripps Research Institute Florida, Jupiter, FL 33458, USA. Electronic address: rdavis@scripps.edu.

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.

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

Substances

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

Abstract

Publication types

MeSH terms

Substances

Grants and funding