The Fragile X Syndrome is the most common cause of inherited mental retardation and is due to the absence of a single protein, the Fragile X Mental Retardation protein (FMRP). FMRP is an RNA-binding protein implicated in the regulation of mRNA transport, translation and stability in neurons. In the absence of FMRP, the expression of a large group of neuronal proteins is deregulated, resulting in impaired synaptic morphology and function. Here, we investigated two critical steps of the posttranscriptional control mediated by FMRP, namely mRNA translation and stability. The modulation of protein synthesis involves the Cytoplasmic FMRP Interacting Protein 1 (CYFIP1), which represses the translation of the mRNAs associated with FMRP. Evidences reported here show that CYFIP1 may be also involved in the transport of the mRNAs and in the interplay between translation and cytoskeleton remodeling. Besides the role in translation, FMRP regulates the decay of certain mRNA in neurons. In particular, FMRP stabilizes the mRNA encoding the PostSynaptic Density Protein 95 (PSD-95) in the hippocampus, but not in cortex. This study describes the molecular complexes associated with PSD-95 mRNA that could account for the region-specific functions of FMRP. In conclusions, this work provides further insights into the FMRP-dependent regulation of gene expression, therefore contributing to the understanding of Fragile X pathogenesis.

De Rubeis, S. (2010). The fragile X mental retardation protein in the regulation of neuronal mRNA translation and stability.

The fragile X mental retardation protein in the regulation of neuronal mRNA translation and stability

DE RUBEIS, SILVIA
2010-01-14

Abstract

The Fragile X Syndrome is the most common cause of inherited mental retardation and is due to the absence of a single protein, the Fragile X Mental Retardation protein (FMRP). FMRP is an RNA-binding protein implicated in the regulation of mRNA transport, translation and stability in neurons. In the absence of FMRP, the expression of a large group of neuronal proteins is deregulated, resulting in impaired synaptic morphology and function. Here, we investigated two critical steps of the posttranscriptional control mediated by FMRP, namely mRNA translation and stability. The modulation of protein synthesis involves the Cytoplasmic FMRP Interacting Protein 1 (CYFIP1), which represses the translation of the mRNAs associated with FMRP. Evidences reported here show that CYFIP1 may be also involved in the transport of the mRNAs and in the interplay between translation and cytoskeleton remodeling. Besides the role in translation, FMRP regulates the decay of certain mRNA in neurons. In particular, FMRP stabilizes the mRNA encoding the PostSynaptic Density Protein 95 (PSD-95) in the hippocampus, but not in cortex. This study describes the molecular complexes associated with PSD-95 mRNA that could account for the region-specific functions of FMRP. In conclusions, this work provides further insights into the FMRP-dependent regulation of gene expression, therefore contributing to the understanding of Fragile X pathogenesis.
A.A. 2009/2010
Biologia molecolare e cellulare
22.
fragile X; synapses; mental retardation; neuron
Settore BIO/11
English
Tesi di dottorato
De Rubeis, S. (2010). The fragile X mental retardation protein in the regulation of neuronal mRNA translation and stability.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/1176
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