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.
authors.affiliation: Dipartimento di Biologia, Università Tor Vergata, Via della Ricerca Scientifica 1, 00133 Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Zalfa
authors.forename: Boris
authors.initials: B
authors.lastname: Eleuteri
authors.forename: Kirsten S
authors.initials: KS
authors.lastname: Dickson
authors.forename: Valentina
authors.initials: V
authors.lastname: Mercaldo
authors.forename: Silvia
authors.initials: S
authors.lastname: De Rubeis
authors.forename: Alessandra
authors.initials: A
authors.lastname: di Penta
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Tabolacci
authors.forename: Pietro
authors.initials: P
authors.lastname: Chiurazzi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Neri
authors.forename: Seth G N
authors.initials: SG
authors.lastname: Grant
authors.forename: Claudia
authors.initials: C
authors.lastname: Bagni
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D000076122:Disks Large Homolog 4 Protein; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D004622:Embryo, Mammalian; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics / Q000502:physiology*; D051528:Guanylate Kinases; D047468:Immunoprecipitation / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism; D014176:Protein Biosynthesis; D020871:RNA Stability / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014162:Transfection; D014404:Tubulin / Q000378:metabolism
chemical_list: D000076122:Disks Large Homolog 4 Protein; D051860:Fragile X Messenger Ribonucleoprotein 1; D051528:Guanylate Kinases; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D014404:Tubulin; C501447:Dlg4 protein, mouse