Résumé :
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Spinal Muscular Atrophy (SMA) is a common neurodegenerative disease caused by reduced levels of the Survival Motor Neuron (SMN) protein. SMN is part of a large ubiquitous protein complex that concentrates in nuclear gems/Cajal bodies (CBs) and participates in the biogenesis of various ribonucleoproteins, including the spliceosomal UsnRNPs (U-rich small nuclear RiboNucleoProteins) and ribosomal processing snoRNPs (small nucleolar RNPs). The newly synthesized UsnRNPs are accumulated and modified in the maturation platform gems/CBs and then are redirected to the splicing messenger RNA sites and in the speekles. It has been also shown that snoRNPs are transported through CBs for modifications and then addressed to nucleoli. The numbers of gems/CBs are in close correlation with the severity of SMA disease. We previously showed that UsnRNPs are not detectable in gems/CBs from immortalized SMA type I-derived fibroblast cells, indicating that UsnRNP maturation pathway is probably inhibited in SMA disease. Here, we have pursued the characterization of residual gems/CBs in immortalized SMA fibroblast cells. We have tested factors transiently accumulating in gems/CBs that are involved in the assembly, maturation and localization of snoRNPs. We have examined those factors using immunofluorescence analyses, transient expression of SMA mutants SMNDex7, 472D5 and E134K and RNA-interference knockdown in HeLa cells. These results will be presented. They should allow a better understanding of the mechanisms underlying the accumulation in gems/CBs and of the functional defect and pathological processes involved in the SMA disease.
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