MicroRNA Regulation of the Synaptic Plasticity-Related Gene Arc

摘要: Expression of activity-regulated cytoskeleton associated protein (Arc) is crucial for diverse types experience-dependent synaptic plasticity and long-term memory in mammals. However, the mechanisms governing Arc-specific translation are little understood. Here, we asked whether Arc regulated by microRNAs. Bioinformatic analysis predicted numerous candidate miRNA binding sites within 3′-untranslated region (UTR). Transfection corresponding microRNAs human embryonic kidney cells inhibited expression an 3′UTR luciferase reporter from between 10 to 70% across 16 tested. Point mutation deletion microRNA-binding seed-region miR-34a, miR-326, miR-19a partially or fully rescued expression. In addition, specific microRNA pairs synergistically modulated primary rat hippocampal neuronal cultures, ectopic miR-193a, downregulated endogenous response BDNF treatment. Conversely, treatment neurons with cell-penetrating, peptide nucleic acid (PNA) inhibitors miR-326 enhanced mRNA dramatically upregulated miR-132, a known BDNF-induced miRNA, without affecting Arc-targeting miRNAs. Developmentally, miR-132 was at day vitro whereas miRNAs were downregulated. adult brain, LTP induction dentate gyrus triggered massive upregulation levels mature Turning examine localization, qPCR synaptoneurosome total lysates fractions demonstrated enrichment relative small nucleolar RNA. conclusion, find that multiple vitro. Furthermore, show that, contrast steady state do not change activity-dependent during vivo.