Résumé :
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Communication n° 6 Autosomal recessive spinal muscular atrophy (SMA) is a disease that is amongst the leading genetic cause of infants death. SMA is caused by disruption of the "survival of motor neurons" gene (Smn1). SMN plays an essential role in RNA metabolism and has been involved in the assembly of various ribonucleoprotein complexes. Despite a large body of work towards clarifying the apparently ubiquitous functions of SMN, the molecular mechanisms that lead to motor neuron-specific pathologies and development of the SMA phenotype remain to be elucidated. We have generated antibodies that can recognize methyl-arginines in proteins. Using these antibodies, we have shown that arginine methylation can regulate the localization of SMN into distinct nuclear organelles known to have a role in RNA metabolism. Moreover, we have shown that SMA patient cells mislocalize arginine methylated proteins. Finally, recent data shows that SMN has more affinity for proteins that harbor methylated arginines. My lab is interested in the regulation of SMN function by arginine methylation in motor neurons and skeletal muscle and how this relates to the development of the SMA phenotype. We have analysed the dynamics of arginine methylation profiles during neuronal and muscle differentiation using immunoblotting and indirect immunofluorescence microscopy with methyl-specific antibodies. Interestingly, we have observed differences in these profiles between wild type and SMA-model mice. We have developed a large scale purification scheme to initiate the identification, using mass spectrometry, of these tissue-specific potential interactors of SMN and we will present the preliminary characterization of a subset of the identified proteins. This approach will most likely reveal invaluable insights into the specific function(s) of SMN in tissues affected by SMA. *This work is supported by grants from "families of SMA" and "Canadian Institutes of Health Research" to J.C.
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