@article{ce13c958e6564b7eac70beb8b0f02173,
title = "A new function for the fragile X mental retardation protein in regulation of PSD-95 mRNA stability",
abstract = "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.",
author = "Francesca Zalfa and Boris Eleuteri and Dickson, {Kirsten S.} and Valentina Mercaldo and {De Rubeis}, Silvia and {Di Penta}, Alessandra and Elisabetta Tabolacci and Pietro Chiurazzi and Giovanni Neri and Grant, {Seth G.N.} and Claudia Bagni",
note = "Funding Information: We thank B.A. Oostra for the FMR1 knockout mice, N.K. Gray and T. Achsel for their critical evaluation of the manuscript, and O. Steward for precious suggestions and reagents. We thank M.A. Kiebler for advice on the neuronal transfection protocol. This research was funded by a European Molecular Biology Organization short-term fellowship, a Royal Society of Edinburgh Scottish Executive Enterprise and Lifelong Learning Department fellowship and a Biotechnology and Biological Sciences Research Council grant (C19143) to K.S.D., by Telethon (GGP05269), Ministero della Salute, Ministero della Universit{\`a} (FIRB) to C.B. and by Wellcome Trust grant number 056523 and the Wellcome Trust Genes to Cognition Programe to S.G.N.G. F.Z. was supported by the Associazione Italiana Sindrome dell{\textquoteright}X Fragile.",
year = "2007",
month = may,
doi = "10.1038/nn1893",
language = "English",
volume = "10",
pages = "578--587",
journal = "Nature Neuroscience",
issn = "1097-6256",
publisher = "Nature Research",
number = "5",
}