Article abstract
Nature Neuroscience 10, 578 - 587 (2007)
Published online: 8 April 2007 | doi:10.1038/nn1893
A new function for the fragile X mental retardation protein in regulation of PSD-95 mRNA stability
Francesca Zalfa1,2,6, Boris Eleuteri1,2,6, Kirsten S Dickson3,6, Valentina Mercaldo1,2, Silvia De Rubeis1,2, Alessandra di Penta2, Elisabetta Tabolacci4, Pietro Chiurazzi4, Giovanni Neri4, Seth G N Grant3,5 & Claudia Bagni1,2
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.
- Dipartimento di Biologia, Università "Tor Vergata", Via della Ricerca Scientifica 1, 00133 Rome, Italy.
- Istituto di Neuroscienze Sperimentali, Fondazione Santa Lucia, Via del Fosso di Fiorano 63, 00143 Rome, Italy.
- Division of Neuroscience, University of Edinburgh, George Sq., Edinburgh EH8 9JZ, UK.
- Istituto di Genetica Medica, Università Cattolica, Largo F. Vito 1, 00168 Rome, Italy.
- Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire CB10 1SA, UK.
- These authors contributed equally to this work.
Correspondence to: Claudia Bagni1,2 e-mail: claudia.bagni@uniroma2.it
Correspondence to: Kirsten S Dickson3,6 e-mail: dickson.kris@gmail.com
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