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

Risultato della ricerca: Contributo in rivistaArticolo in rivista

Abstract

Fragile X Syndrome results from loss of the Fragile X mental retardation protein (FMRP), an RNA-binding protein regulating a variety of cytoplasmic mRNAs. FMRP regulates mRNA translation and has been suggested to play a role in mRNA localization to dendrites. We report a third cytoplasmic regulatory function for FMRP – control of mRNA stability. We find in mice that FMRP binds, in vivo, the mRNA encoding PSD-95, a key molecule regulating neuronal synaptic signalling and learning. This interaction occurs through the 3′ untranslated region of the PSD–95 mRNA, increasing message stability. Moreover, stabilization is further increased by mGluR activation. While we also find 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 misregulation of mRNA stability may contribute to the cognitive impairments in Fragile X Syndrome patients.
Lingua originaleEnglish
pagine (da-a)578-587
Numero di pagine10
RivistaNature Neuroscience
Volume10
DOI
Stato di pubblicazionePubblicato - 2007

Keywords

  • Fragile X Mental Retardation Protein, PSD-95, G-quartet, U-rich regions, ARE, dendritic mRNA, mRNA stability

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