The Splicing of the Mitochondrial Calcium Uniporter Genuine Activator MICU1 Is Driven by RBFOX2 Splicing Factor during Myogenic Differentiation.
Int J Mol Sci
; 23(5)2022 Feb 24.
Article
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| MEDLINE
| ID: mdl-35269658
ABSTRACT
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 Ca2+ homeostasis genes are also regulated by alternative splicing mechanisms, among which is the Mitochondrial Ca2+ 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 Ca2+ 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 Ca2+ 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 Ca2+ among tissues.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Represoras
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Proteínas de Unión al Calcio
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Proteínas de Transporte de Catión
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Proteínas de Transporte de Membrana Mitocondrial
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Factores de Empalme de ARN
Límite:
Humans
Idioma:
En
Revista:
Int J Mol Sci
Año:
2022
Tipo del documento:
Article
País de afiliación:
Italia