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

Francesca Zalfa, Boris Eleuteri, Kirsten S. Dickson, Valentina Mercaldo, Silvia De Rubeis, Alessandra Di Penta, Elisabetta Tabolacci, Pietro Chiurazzi, Giovanni Neri, Seth G.N. Grant, Claudia Bagni

Research output: Contribution to journalArticlepeer-review

302 Scopus citations

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.

Original languageEnglish
Pages (from-to)578-587
Number of pages10
JournalNature Neuroscience
Volume10
Issue number5
DOIs
StatePublished - May 2007
Externally publishedYes

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