| Autor: |
Vecellio Reane D; Department of Biomedical Sciences, University of Padova, 35131 Padova, Italy., Cerqua C; Clinical Genetics Unit, Department of Women's and Children's Health, University of Padova, Via Giustiniani 3, 35128 Padova, Italy.; Istituto di Ricerca Pediatrica-IRP, Fondazione Città della Speranza, 35127 Padova, Italy., Sacconi S; Centre Hospitalier Universitaire de Nice, Peripheral Nervous System and Muscle Department, Rare Neuromuscular Disease Reference Center, ERN-Euro-NMD, Université Côte d'Azur (UCA), 06103 Nice, France., Salviati L; Clinical Genetics Unit, Department of Women's and Children's Health, University of Padova, Via Giustiniani 3, 35128 Padova, Italy.; Istituto di Ricerca Pediatrica-IRP, Fondazione Città della Speranza, 35127 Padova, Italy.; Myology Center, University of Padova, 35131 Padova, Italy., Trevisson E; Clinical Genetics Unit, Department of Women's and Children's Health, University of Padova, Via Giustiniani 3, 35128 Padova, Italy.; Istituto di Ricerca Pediatrica-IRP, Fondazione Città della Speranza, 35127 Padova, Italy., Raffaello A; Department of Biomedical Sciences, University of Padova, 35131 Padova, Italy.; Myology Center, University of Padova, 35131 Padova, Italy. |
| Abstrakt: |
Alternative splicing, the process by which exons within a pre-mRNA transcript are differentially joined or skipped, is crucial in skeletal muscle since it is required both during myogenesis and in post-natal life to reprogram the transcripts of contractile proteins, metabolic enzymes, and transcription factors in functionally distinct muscle fiber types. The importance of such events is underlined by the numerosity of pathological conditions caused by alternative splicing aberrations. Importantly, many skeletal muscle Ca 2+ homeostasis genes are also regulated by alternative splicing mechanisms, among which is the Mitochondrial Ca 2+ Uniporter (MCU) genuine activator MICU1 which regulates MCU opening upon cell stimulation. We have previously shown that murine skeletal muscle MICU1 is subjected to alternative splicing, thereby generating a splice variant-which was named MICU1.1-that confers unique properties to the mitochondrial Ca 2+ uptake and ensuring sufficient ATP production for muscle contraction. Here we extended the analysis of MICU1 alternative splicing to human tissues, finding two additional splicing variants that were characterized by their ability to regulate mitochondrial Ca 2+ uptake. Furthermore, we found that MICU1 alternative splicing is induced during myogenesis by the splicing factor RBFOX2. These results highlight the complexity of the alternative splicing mechanisms in skeletal muscle and the regulation of mitochondrial Ca 2+ among tissues. |
