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.

Zalfa, F., Eleuteri, B., Dickson, K.S., Mercaldo, V., De Rubeis, S., Di Penta, A., et al. (2007). A new function for the fragile X mental retardation protein in regulation of PSD-95 mRNA stability. NATURE NEUROSCIENCE, 10(5), 578-587 [10.1038/nn1893].

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

BAGNI, CLAUDIA
2007

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.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/13
English
Con Impact Factor ISI
fragile X mental retardation protein; messenger RNA; postsynaptic density protein 95; 3' untranslated region; animal cell; animal tissue; article; cognitive defect; controlled study; cytoplasm; fragile X syndrome; functional assessment; gene control; gene location; learning; male; mouse; nerve cell; nonhuman; nucleotide sequence; priority journal; protein function; protein targeting; receptor upregulation; regulatory mechanism; RNA stability; signal transduction; synaptic transmission; tissue distribution; Animals; Brain; Cell Survival; Cells, Cultured; Electrophoretic Mobility Shift Assay; Embryo; Fragile X Mental Retardation Protein; Immunoprecipitation; In Situ Hybridization; Intracellular Signaling Peptides and Proteins; Male; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Neurons; Protein Biosynthesis; Reverse Transcriptase Polymerase Chain Reaction; RNA Stability; RNA, Messenger; Transfection; Tubulin
Zalfa, F., Eleuteri, B., Dickson, K.S., Mercaldo, V., De Rubeis, S., Di Penta, A., et al. (2007). A new function for the fragile X mental retardation protein in regulation of PSD-95 mRNA stability. NATURE NEUROSCIENCE, 10(5), 578-587 [10.1038/nn1893].
Zalfa, F; Eleuteri, B; Dickson, K; Mercaldo, V; De Rubeis, S; Di Penta, A; Tabolacci, E; Chiurazzi, P; Neri, G; Grant, S; Bagni, C
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/29180
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