Neuronal BC RNAs cooperate with eIF4B to mediate activity-dependent translational control

• Published in: The Journal of cell biology Vol. 207; no. 2; pp. 237 - 252
• Main Authors: Eom, Taesun, Muslimov, Ilham A, Tsokas, Panayiotis, Berardi, Valerio, Zhong, Jun, Sacktor, Todd C, Tiedge, Henri
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 27-10-2014; The Rockefeller University Press
• Subjects: 5' Untranslated Regions; Animals; Binding sites; Cell Line; Enzyme kinetics; Eukaryotic Initiation Factors - metabolism; Eukaryotic Initiation Factors - physiology; Female; Gene Expression Regulation; Kinases; Male; Mice; Models, Genetic; Neurons; Neurons - cytology; Neurons - metabolism; Neurons - ultrastructure; Phosphorylation; Protein Biosynthesis; Rats, Sprague-Dawley; Ribonucleic acid; Ribosome Subunits, Small, Eukaryotic - metabolism; Ribosome Subunits, Small, Eukaryotic - physiology; RNA; RNA, Messenger - metabolism; RNA, Small Cytoplasmic - metabolism; RNA, Small Cytoplasmic - physiology; Sf9 Cells; Signal Transduction
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.201401005

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.