Résumé :
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The common neurodegenerative disease spinal muscular atrophy (SMA) is caused by reduced levels of the survival of motor neuron (SMN) protein. SMN associates with several proteins to form a large complex that is essential for the assembly and metabolism of spliceosomal U snRNPs. It is still not understood why reduced levels of the ubiquitously expressed SMN protein specifically cause motor neuron degeneration. Recently, several lines of evidence support additional neuron-specific functions of SMN in mRNA transport and translation regulation in neuronal processes. FMRP (Fragile X Mental Retardation Portein), the defective protein in Fragile X mental retardation syndrome, is thought to play a role in the transport of mRNPs from the nucleus to the cytoplasm and may be crucial in neurons to repress translation of specific mRNAs during their transport as silent mRNPs from the cell body to growth cones and synapses. Therefore, we examined possible relationships of SMN with FMRP. We observed granules containing both transiently expressed RFP-tagged SMN and GFP-tagged FMRP in cell bodies and processes of rat primary neurons of hypothalamus in culture. By immunoprecipitation experiment, we detected an association of FMRP with the SMN complex in human neuroblastoma SH-SY5Y cells and in murine motor neuron MN-1 cells. Then, by in vitro experiments, we demonstrated that the SMN protein is essential for this association. We showed that the C-terminal region of FMRP, as well as the conserved YG box and the region encoded by exon7 of SMN, are required for the interaction. Our findings suggest a link between the SMN complex and FMRP in neuronal cells.
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