title: Selective localization of arc mRNA in dendrites involves activity- and translation-dependent mRNA degradation.
abstract: Arc is an immediate early gene that is unique among neuronal mRNAs because its transcripts are transported into dendrites and accumulate near activated synapses, presumably to be translated locally. These qualities pose Arc as playing an important, yet not fully understood, role in the activity-dependent modifications of synapses that are thought to underlie memory storage. Here we show in vivo in rats that newly synthesized Arc mRNA accumulates at activated synapses and that synaptic activity simultaneously triggers mRNA decay that eliminates Arc mRNA from inactive dendritic domains. Arc mRNA degradation occurs throughout the dendrite and requires both NMDA receptor activation and active translation. Synaptic activation did not lead to decreases in another dendritic mRNA (αCaMKII), indicating that there is not a general activation of mRNA degradation in dendrites. These data reveal a novel mechanism for controlling mRNA distribution within dendrites and highlight activity-dependent mRNA degradation as a regulatory process involved in synaptic plasticity.
authors.affiliation: Reeve-Irvine Research Center and Departments of Anatomy and Neurobiology, Neurobiology and Behavior, and Neurosurgery, University of California, Irvine, Irvine, California 92697.
authors.forename: Shannon
authors.initials: S
authors.lastname: Farris
authors.forename: Gail
authors.initials: G
authors.lastname: Lewandowski
authors.forename: Conor D
authors.initials: CD
authors.lastname: Cox
authors.forename: Oswald
authors.initials: O
authors.lastname: Steward
mesh_terms: D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics*; D003712:Dendrites / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists; D005260:Female; D007839:Functional Laterality; D005786:Gene Expression Regulation / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009474:Neurons / Q000166:cytology*; D020871:RNA Stability / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013569:Synapses / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D003598:Cytoskeletal Proteins; D018691:Excitatory Amino Acid Antagonists; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C092069:activity regulated cytoskeletal-associated protein; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2
keywords: Arc/Arg3.1; NMDA receptors; mRNA degradation; mRNA localization; protein synthesis; synapse