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

被引：285

作者：

Zalfa, Francesca

Eleuteri, Boris

Dickson, Kirsten S.

Mercaldo, Valentina

De Rubeis, Silvia

di Penta, Alessandra

Tabolacci, Elisabetta

Chiurazzi, Pietro

Neri, Giovanni

Grant, Seth G. N.

Bagni, Claudia

机构：

[1] Univ Roma Tor Vergata, Dipartimento Biol, I-00133 Rome, Italy

[2] Fdn Santa Lucia, Ist Neurosci Sperimentali, I-00143 Rome, Italy

[3] Univ Edinburgh, Div Neurosci, Edinburgh EH8 9JZ, Midlothian, Scotland

[4] Univ Cattolica, Ist Genet Med, I-00168 Rome, Italy

[5] Wellcome Trust Res Labs, Sanger Inst, Hinxton CB10 1SA, Cambs, England

来源：

NATURE NEUROSCIENCE | 2007年 / 10卷 / 05期

基金：

英国惠康基金;

关键词：

D O I：

10.1038/nn1893

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页码：578 / 587

页数：10

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