Alteration of expression of muscle specific isoforms of the fragile X related protein 1 (FXR1P) in facioscapulohumeral muscular dystrophy patients
| العنوان: | Alteration of expression of muscle specific isoforms of the fragile X related protein 1 (FXR1P) in facioscapulohumeral muscular dystrophy patients |
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| المؤلفون: | Laetitia Davidovic, Severine Delplace, Sabrina Sacconi, Marilyn Allegra, Elias Bechara, Claude Desnuelle, Barbara Bardoni |
| المساهمون: | Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), CHU Nice, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA) |
| المصدر: | Journal of Medical Genetics Journal of Medical Genetics, BMJ Publishing Group, 2008, epub ahead of print. ⟨10.1136/jmg.2008.060541⟩ |
| سنة النشر: | 2008 |
| مصطلحات موضوعية: | Muscle Fibers, Skeletal, Gene Expression, RNA-binding protein, Biology, Myoblasts, 03 medical and health sciences, Fragile X Mental Retardation Protein, 0302 clinical medicine, Genetics, medicine, Facioscapulohumeral muscular dystrophy, Humans, Protein Isoforms, Muscular dystrophy, Myopathy, Genetics (clinical), 030304 developmental biology, 0303 health sciences, Myogenesis, RNA-Binding Proteins, medicine.disease, FMR1, Muscular Dystrophy, Facioscapulohumeral, Cell biology, Fragile X syndrome, Alternative Splicing, RNA splicing, medicine.symptom, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology |
| الوصف: | Background: The Fragile X Mental retardation-Related 1 ( FXR1 ) gene belongs to the fragile X related family, that also includes the Fragile X Mental Retardation ( FMR1 ) gene involved in fragile X syndrome, the most common form of inherited mental retardation. While the absence of FMRP impairs cognitive functions, inactivation of FXR1 has been reported to have drastic effects in mouse and xenopus myogenesis. Seven alternatively spliced FXR1 mRNA variants have been identified, three of them being muscle specific. Interestingly, they encode FXR1P isoforms displaying selective RNA binding properties. Methods and results: Since facioscapulohumeral muscular dystrophy (FSHD) is an inherited myopathy characterised by altered splicing of mRNAs encoding muscle specific proteins, we have studied the splicing pattern of FXR1 mRNA in myoblasts and myotubes of FSHD patients. We show here that FSHD myoblasts display an abnormal pattern of expression of FXR1P isoforms. Moreover, we provide evidence that this altered pattern of expression is due to a specific reduced stability of muscle specific FXR1 mRNA variants, leading to a reduced expression of FXR1P muscle specific isoforms. Conclusion: Our data suggest that the molecular basis of FSHD not only involves splicing alterations, as previously proposed, but may also involve a deregulation of mRNA stability. In addition, since FXR1P is an RNA binding protein likely to regulate the metabolism of muscle specific mRNAs during myogenesis, its altered expression in FSHD myoblasts may contribute to the physiopathology of this disease. |
| تدمد: | 1468-6244 0022-2593 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ff06aac9ac771707e4f41ff9d3e54b9fTest https://pubmed.ncbi.nlm.nih.gov/18628314Test |
| رقم الانضمام: | edsair.doi.dedup.....ff06aac9ac771707e4f41ff9d3e54b9f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14686244 00222593 |
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