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1 Acta Neurobiologiae Experimentalis

1 2013

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Dynamic regulation of mRNA translation in neurons by FMRP and microRNAs

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Muddashetty R. , Gross C. , Yao Y. , Nalavadi N. , Warren S. T. , Bassell G. J.

nr Suppl.1

Long term synaptic plasticity underlying learning and memory is believed to require the reversible and dynamic regulation of local protein synthesis, which is dysregulated in fragile x syndrome, the most common form of inherited intellectual disability and autism. Fragile x syndrome is caused by the loss of the Fragile X Mental Retardation, FMRP, an mRNA binding protein involved in the regulation of local protein synthesis at synapses. We elucidated a cooperative role and dynamic interaction between the Fragile X Mental Retardation, FMRP, and microRNAs to repress translation at synapses, which can be rapidly de-repressed in response to activation of gp1 metabotropic glutamate receptors. One FMRP target mRNA of interest has been postsynaptic density-95, PSD-95, which is localized to dendrites and can be translated at synapses in response to activation of mGluRs. More recent work has revealed the role of other microRNAs to regulate FMRP target mRNA translation that appears important for control of neuronal excitability. We speculate that fragile x syndrome may result from synaptic protein imbalances due to dysregulation of microRNAmediated control that is important for control of neuronal development, excitability and plasticity.