title: Neuronal BC RNAs cooperate with eIF4B to mediate activity-dependent translational control.
abstract: In neurons, translational regulation of gene expression has been implicated in the activity-dependent management of synapto-dendritic protein repertoires. However, the fundamentals of stimulus-modulated translational control in neurons remain poorly understood. Here we describe a mechanism in which regulatory brain cytoplasmic (BC) RNAs cooperate with eukaryotic initiation factor 4B (eIF4B) to control translation in a manner that is responsive to neuronal activity. eIF4B is required for the translation of mRNAs with structured 5' untranslated regions (UTRs), exemplified here by neuronal protein kinase Mζ (PKMζ) mRNA. Upon neuronal stimulation, synapto-dendritic eIF4B is dephosphorylated at serine 406 in a rapid process that is mediated by protein phosphatase 2A. Such dephosphorylation causes a significant decrease in the binding affinity between eIF4B and BC RNA translational repressors, enabling the factor to engage the 40S small ribosomal subunit for translation initiation. BC RNA translational control, mediated via eIF4B phosphorylation status, couples neuronal activity to translational output, and thus provides a mechanistic basis for long-term plastic changes in nerve cells.
authors.affiliation: Department of Physiology and Pharmacology, Department of Anesthesiology, and Department of Neurology, The Robert F. Furchgott Center for Neural and Behavioral Science, SUNY Downstate Medical Center, Brooklyn, NY 11203.
authors.forename: Taesun
authors.initials: T
authors.lastname: Eom
authors.affiliation: Department of Physiology and Pharmacology, Department of Anesthesiology, and Department of Neurology, The Robert F. Furchgott Center for Neural and Behavioral Science, SUNY Downstate Medical Center, Brooklyn, NY 11203.
authors.forename: Ilham A
authors.initials: IA
authors.lastname: Muslimov
authors.affiliation: Department of Physiology and Pharmacology, Department of Anesthesiology, and Department of Neurology, The Robert F. Furchgott Center for Neural and Behavioral Science, SUNY Downstate Medical Center, Brooklyn, NY 11203 Department of Physiology and Pharmacology, Department of Anesthesiology, and Department of Neurology, The Robert F. Furchgott Center for Neural and Behavioral Science, SUNY Downstate Medical Center, Brooklyn, NY 11203.
authors.forename: Panayiotis
authors.initials: P
authors.lastname: Tsokas
authors.affiliation: Department of Physiology and Pharmacology, Department of Anesthesiology, and Department of Neurology, The Robert F. Furchgott Center for Neural and Behavioral Science, SUNY Downstate Medical Center, Brooklyn, NY 11203.
authors.forename: Valerio
authors.initials: V
authors.lastname: Berardi
authors.affiliation: Department of Physiology and Pharmacology, Department of Anesthesiology, and Department of Neurology, The Robert F. Furchgott Center for Neural and Behavioral Science, SUNY Downstate Medical Center, Brooklyn, NY 11203.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Department of Physiology and Pharmacology, Department of Anesthesiology, and Department of Neurology, The Robert F. Furchgott Center for Neural and Behavioral Science, SUNY Downstate Medical Center, Brooklyn, NY 11203 Department of Physiology and Pharmacology, Department of Anesthesiology, and Department of Neurology, The Robert F. Furchgott Center for Neural and Behavioral Science, SUNY Downstate Medical Center, Brooklyn, NY 11203 Department of Physiology and Pharmacology, Department of Anesthesiology, and Department of Neurology, The Robert F. Furchgott Center for Neural and Behavioral Science, SUNY Downstate Medical Center, Brooklyn, NY 11203.
authors.forename: Todd C
authors.initials: TC
authors.lastname: Sacktor
authors.affiliation: Department of Physiology and Pharmacology, Department of Anesthesiology, and Department of Neurology, The Robert F. Furchgott Center for Neural and Behavioral Science, SUNY Downstate Medical Center, Brooklyn, NY 11203 Department of Physiology and Pharmacology, Department of Anesthesiology, and Department of Neurology, The Robert F. Furchgott Center for Neural and Behavioral Science, SUNY Downstate Medical Center, Brooklyn, NY 11203 henri.tiedge@downstate.edu.
authors.forename: Henri
authors.initials: H
authors.lastname: Tiedge
mesh_terms: D020121:5' Untranslated Regions; D000818:Animals; D002460:Cell Line; D039642:Eukaryotic Initiation Factors / Q000378:metabolism / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008957:Models, Genetic; D009474:Neurons / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D010766:Phosphorylation; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism*; D020733:RNA, Small Cytoplasmic / Q000378:metabolism / Q000502:physiology*; D017207:Rats, Sprague-Dawley; D054682:Ribosome Subunits, Small, Eukaryotic / Q000378:metabolism / Q000502:physiology; D061987:Sf9 Cells; D015398:Signal Transduction
chemical_list: D020121:5' Untranslated Regions; C117734:BC1 RNA; D039642:Eukaryotic Initiation Factors; D012333:RNA, Messenger; D020733:RNA, Small Cytoplasmic; C031799:eIF-4B