Psd-95 Mrna Translation Regulation By The Fragile X Mental Retardation Protein

Fragile X syndrome (FXS) is an inherited disease caused by a trinucleotide expansion on X the chromosome that silences the expression of the Fragile X Mental Retardation protein (FMRP). Individuals affected by FXS show different intensity of mental impairment and learning disabilities depending on the mutation severity. FMRP is an RNA binding protein which has been shown to bind to a G rich region of PSD-95 mRNA that encodes for Post Synaptic Density Protein (PSD-95). It has been shown that in complex with a specific microRNA (miR-125a) FMRP plays an important role in the reversible inhibition of PSD-95 mRNA translation. The loss of FMRP disables this translation control that consecutively causes an excessive production of the PSD-95 protein. The goal of this project was to investigate at the molecular level the biological role of both FMRP and microRNA in PSD-95 mRNA translation pathway. We have used different biophysical techniques to demonstrate that the PSD-95 mRNA region predicted to be bound by FMRP folds into G quadruplex structures and to analyze its binding by the protein.