A new function for the fragile X mental retardation protein in regulation of PSD-95 mRNA stability

Autor:	Alessandra di Penta, Pietro Chiurazzi, Seth G. N. Grant, Kirsten S. Dickson, Claudia Bagni, Valentina Mercaldo, Giovanni Neri, Francesca Zalfa, Silvia De Rubeis, Boris Eleuteri, Elisabetta Tabolacci
Rok vydání:	2007
Předmět:	Male Untranslated region RNA Stability tissue distribution Messenger fragile X mental retardation protein messenger RNA postsynaptic density protein 95 3' untranslated region animal cell animal tissue article cognitive defect controlled study cytoplasm fragile X syndrome functional assessment gene control gene location learning male mouse nerve cell nonhuman nucleotide sequence priority journal protein function protein targeting receptor upregulation regulatory mechanism RNA stability signal transduction synaptic transmission Animals Brain Cell Survival Cells Cultured Electrophoretic Mobility Shift Assay Embryo Fragile X Mental Retardation Protein Immunoprecipitation In Situ Hybridization Intracellular Signaling Peptides and Proteins Membrane Proteins Mice Mice Inbred C57BL Mice Knockout Neurons Protein Biosynthesis Reverse Transcriptase Polymerase Chain Reaction RNA Messenger Transfection Tubulin translation Inbred C57BL fmrp Protein biosynthesis alzheimers-disease mechanisms Cultured General Neuroscience Settore BIO/13 Neurodegeneration Translation (biology) Fragile X syndrome binding proteins Disks Large Homolog 4 Protein congenital hereditary and neonatal diseases and abnormalities nmda receptor mice Cells Knockout Biology Article medicine Messenger RNA synaptic plasticity Embryo Mammalian medicine.disease nervous system diseases Synaptic plasticity RNA identification synapses Guanylate Kinases Neuroscience
Zdroj:	Nature Neuroscience. 10:578-587
ISSN:	1546-1726 1097-6256
DOI:	10.1038/nn1893
Popis:	Fragile X syndrome ( FXS) results from the loss of the fragile X mental retardation protein ( FMRP), an RNA- binding protein that regulates a variety of cytoplasmic mRNAs. FMRP regulates mRNA translation and may be important in mRNA localization to dendrites. We report a third cytoplasmic regulatory function for FMRP: control of mRNA stability. In mice, we found that FMRP binds, in vivo, the mRNA encoding PSD- 95, a key molecule that regulates neuronal synaptic signaling and learning. This interaction occurs through the 3' untranslated region of the PSD- 95 ( also known as Dlg4) mRNA, increasing message stability. Moreover, stabilization is further increased by mGluR activation. Although we also found that the PSD- 95 mRNA is synaptically localized in vivo, localization occurs independently of FMRP. Through our functional analysis of this FMRP target we provide evidence that dysregulation of mRNA stability may contribute to the cognitive impairments in individuals with FXS. ispartof: Nature neuroscience vol:10 issue:5 pages:578-587 ispartof: location:United States status: published
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::97e57207cbb388a6ad829d07c095d7f8 https://doi.org/10.1038/nn1893 Zobrazit plný text záznamu Plný text ve formátu PDF