title: Systematic identification of 3'-UTR regulatory elements in activity-dependent mRNA stability in hippocampal neurons.
abstract: Ongoing neuronal activity during development and plasticity acts to refine synaptic connections and contributes to the induction of plasticity and ultimately long-term memory storage. Activity-dependent, post-transcriptional control of mRNAs occurs through transport to axonal and dendritic compartments, local translation and mRNA stability. We have identified a mechanism that contributes to activity-dependent regulation of mRNA stability during synaptic plasticity in rat hippocampal neurons. In this study, we demonstrate rapid, post-transcriptional control over process-enriched mRNAs by neuronal activity. Systematic analysis of the 3'-UTRs of destabilized transcripts, identifies enrichment in sequence motifs corresponding to microRNA (miRNA)-binding sites. The miRNAs that were identified, miR-326-3p/miR-330-5p, miR-485-5p, miR-666-3p and miR-761 are predicted to regulate networks of genes important in plasticity and development. We find that these miRNAs are developmentally regulated in the hippocampus, many increasing by postnatal day 14. We further find that miR-485-5p controls NGF-induced neurite outgrowth in PC12 cells, tau expression and axonal development in hippocampal neurons. miRNAs can function at the synapse to rapidly control and affect short- and long-term changes at the synapse. These processes likely occur during refinement of synaptic connections and contribute to the induction of plasticity and learning and memory.
authors.affiliation: Section on Nervous System Development and Plasticity, The Eunice Kennedy Shriver National Institute of Child and Human Development, National Institute of Health, Building 35, Room 2A211, Bethesda, MD 20892-3714, USA.
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Cohen
authors.affiliation: Section on Nervous System Development and Plasticity, The Eunice Kennedy Shriver National Institute of Child and Human Development, National Institute of Health, Building 35, Room 2A211, Bethesda, MD 20892-3714, USA.
authors.forename: Philip R
authors.initials: PR
authors.lastname: Lee
authors.affiliation: Section on Nervous System Development and Plasticity, The Eunice Kennedy Shriver National Institute of Child and Human Development, National Institute of Health, Building 35, Room 2A211, Bethesda, MD 20892-3714, USA fieldsd@mail.nih.gov.
authors.forename: R Douglas
authors.initials: RD
authors.lastname: Fields
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D063990:Gene Ontology; D006624:Hippocampus / Q000166:cytology*; D008055:Lipids; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D046228:Microarray Analysis; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D020871:RNA Stability / Q000235:genetics / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050436:Regulatory Elements, Transcriptional / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D020413:3' Untranslated Regions; D008055:Lipids; C086724:Lipofectamine; D035683:MicroRNAs
keywords: 3′-UTR; activity-dependent plasticity; mRNA stability; miRNA