Résumé :
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The Fragile X Mental Retardation-Related Protein 1 (FXR1P) is an RNA binding protein belonging to the Fragile X Related family, together with the Fragile X mentalRetardation Protein (FMRP). Seven alternatively spliced FXR1P isoforms have been identified. Three isoforms are muscle-specific and we have shown that they displayselective RNA-binding properties, compared to shorter ubiquitous isoforms (Bechara et al., 2006). While the absence of FMRP causes Fragile X syndrome, the mostcommon form of inherited mental retardation, inactivation of FXR1 in mouse or Xenopus is embryonic lethal due to a strong impairment of myogenesis. We have reportedan altered splicing pattern of muscle-specific FXR1 mRNA variants in myoblasts derived from patients affected by the inherited myopathy facio-scapulo humeral musculardistrophy (FSHD) (Davidovic et al., 2008). To gain further insights on the roles of FXR1P during myogenesis, we have now repressed FXR1 by RNAi in the C2C12myoblast model. Then, we have studied the consequences of FXR1 deficiency in this model by transcriptomic and proteomics approaches to identify the mRNA targetsand protein interactors of FXR1P. Our data reveal that FXR1P deficiency affect selective pathways involved in the myoblast to myotube transition as well as muscledifferentiation.
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