title: FXR1P limits long-term memory, long-lasting synaptic potentiation, and de novo GluA2 translation.
abstract: Translational control of mRNAs allows for rapid and selective changes in synaptic protein expression that are required for long-lasting plasticity and memory formation in the brain. Fragile X Related Protein 1 (FXR1P) is an RNA-binding protein that controls mRNA translation in nonneuronal cells and colocalizes with translational machinery in neurons. However, its neuronal mRNA targets and role in the brain are unknown. Here, we demonstrate that removal of FXR1P from the forebrain of postnatal mice selectively enhances long-term storage of spatial memories, hippocampal late-phase long-term potentiation (L-LTP), and de novo GluA2 synthesis. Furthermore, FXR1P binds specifically to the 5' UTR of GluA2 mRNA to repress translation and limit the amount of GluA2 that is incorporated at potentiated synapses. This study uncovers a mechanism for regulating long-lasting synaptic plasticity and spatial memory formation and reveals an unexpected divergent role of FXR1P among Fragile X proteins in brain plasticity.
authors.affiliation: Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, The Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, QC H3G 1A4, Canada.
authors.forename: Denise
authors.initials: D
authors.lastname: Cook
authors.affiliation: Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, The Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, QC H3G 1A4, Canada.
authors.forename: Erin
authors.initials: E
authors.lastname: Nuro
authors.affiliation: Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, The Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, QC H3G 1A4, Canada.
authors.forename: Emma V
authors.initials: EV
authors.lastname: Jones
authors.affiliation: Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, The Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, QC H3G 1A4, Canada.
authors.forename: Haider F
authors.initials: HF
authors.lastname: Altimimi
authors.affiliation: Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, The Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, QC H3G 1A4, Canada.
authors.forename: W Todd
authors.initials: WT
authors.lastname: Farmer
authors.affiliation: Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, and Department of Oncology, McGill University, Montreal, QC H3T 1E2, Canada.
authors.forename: Valentina
authors.initials: V
authors.lastname: Gandin
authors.affiliation: Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, The Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, QC H3G 1A4, Canada.
authors.forename: Edith
authors.initials: E
authors.lastname: Hanna
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Ruiting
authors.initials: R
authors.lastname: Zong
authors.affiliation: Department of Molecular and Translational Medicine, National Institute of Neuroscience, University of Brescia, Brescia 25123, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Barbon
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: David L
authors.initials: DL
authors.lastname: Nelson
authors.affiliation: Lady Davis Institute for Medical Research, Sir Mortimer B. Davis Jewish General Hospital, and Department of Oncology, McGill University, Montreal, QC H3T 1E2, Canada.
authors.forename: Ivan
authors.initials: I
authors.lastname: Topisirovic
authors.affiliation: Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Verdun, QC H4H 1R3, Canada.
authors.forename: Joseph
authors.initials: J
authors.lastname: Rochford
authors.affiliation: Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, The Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, QC H3G 1A4, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Stellwagen
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Béïque
authors.affiliation: Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, The Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, QC H3G 1A4, Canada.
authors.forename: Keith K
authors.initials: KK
authors.lastname: Murai
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D000818:Animals; D001522:Behavior, Animal; D017774:Long-Term Potentiation; D057567:Memory, Long-Term; D018345:Mice, Knockout; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism*; D018091:Receptors, AMPA / Q000096:biosynthesis*; D013569:Synapses / Q000378:metabolism*
chemical_list: D020121:5' Untranslated Regions; C496283:Fxr1h protein, mouse; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D018091:Receptors, AMPA; C104722:glutamate receptor ionotropic, AMPA 2