Rbm24 displays dynamic functions required for myogenic differentiation during muscle regeneration

Abstract Skeletal muscle has a remarkable capacity of regeneration after injury, but the regulatory network underlying this repair process remains elusive. RNA-binding proteins play key roles in the post-transcriptional regulation of gene expression and the maintenance of tissue homeostasis and plas...

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Autores principales: Raphaëlle Grifone, Audrey Saquet, Manon Desgres, Claudia Sangiorgi, Caterina Gargano, Zhenlin Li, Dario Coletti, De-Li Shi
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Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/7e2df0f3ea7e404ead019033bc8f3956
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spelling oai:doaj.org-article:7e2df0f3ea7e404ead019033bc8f39562021-12-02T16:49:07ZRbm24 displays dynamic functions required for myogenic differentiation during muscle regeneration10.1038/s41598-021-88563-32045-2322https://doaj.org/article/7e2df0f3ea7e404ead019033bc8f39562021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88563-3https://doaj.org/toc/2045-2322Abstract Skeletal muscle has a remarkable capacity of regeneration after injury, but the regulatory network underlying this repair process remains elusive. RNA-binding proteins play key roles in the post-transcriptional regulation of gene expression and the maintenance of tissue homeostasis and plasticity. Rbm24 regulates myogenic differentiation during early development, but its implication in adult muscle is poorly understood. Here we show that it exerts multiple functions in muscle regeneration. Consistent with its dynamic subcellular localization during embryonic muscle development, Rbm24 also displays cytoplasm to nucleus translocation during C2C12 myoblast differentiation. In adult mice, Rbm24 mRNA is enriched in slow-twitch muscles along with myogenin mRNA. The protein displays nuclear localization in both slow and fast myofibers. Upon injury, Rbm24 is rapidly upregulated in regenerating myofibers and accumulates in the myonucleus of nascent myofibers. Through satellite cell transplantation, we demonstrate that Rbm24 functions sequentially to regulate myogenic differentiation and muscle regeneration. It is required for myogenin expression at early stages of muscle injury and for muscle-specific pre-mRNA alternative splicing at late stages of regeneration. These results identify Rbm24 as a multifaceted regulator of myoblast differentiation. They provide insights into the molecular pathway orchestrating the expression of myogenic factors and muscle functional proteins during regeneration.Raphaëlle GrifoneAudrey SaquetManon DesgresClaudia SangiorgiCaterina GarganoZhenlin LiDario ColettiDe-Li ShiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Raphaëlle Grifone
Audrey Saquet
Manon Desgres
Claudia Sangiorgi
Caterina Gargano
Zhenlin Li
Dario Coletti
De-Li Shi
Rbm24 displays dynamic functions required for myogenic differentiation during muscle regeneration
description Abstract Skeletal muscle has a remarkable capacity of regeneration after injury, but the regulatory network underlying this repair process remains elusive. RNA-binding proteins play key roles in the post-transcriptional regulation of gene expression and the maintenance of tissue homeostasis and plasticity. Rbm24 regulates myogenic differentiation during early development, but its implication in adult muscle is poorly understood. Here we show that it exerts multiple functions in muscle regeneration. Consistent with its dynamic subcellular localization during embryonic muscle development, Rbm24 also displays cytoplasm to nucleus translocation during C2C12 myoblast differentiation. In adult mice, Rbm24 mRNA is enriched in slow-twitch muscles along with myogenin mRNA. The protein displays nuclear localization in both slow and fast myofibers. Upon injury, Rbm24 is rapidly upregulated in regenerating myofibers and accumulates in the myonucleus of nascent myofibers. Through satellite cell transplantation, we demonstrate that Rbm24 functions sequentially to regulate myogenic differentiation and muscle regeneration. It is required for myogenin expression at early stages of muscle injury and for muscle-specific pre-mRNA alternative splicing at late stages of regeneration. These results identify Rbm24 as a multifaceted regulator of myoblast differentiation. They provide insights into the molecular pathway orchestrating the expression of myogenic factors and muscle functional proteins during regeneration.
format article
author Raphaëlle Grifone
Audrey Saquet
Manon Desgres
Claudia Sangiorgi
Caterina Gargano
Zhenlin Li
Dario Coletti
De-Li Shi
author_facet Raphaëlle Grifone
Audrey Saquet
Manon Desgres
Claudia Sangiorgi
Caterina Gargano
Zhenlin Li
Dario Coletti
De-Li Shi
author_sort Raphaëlle Grifone
title Rbm24 displays dynamic functions required for myogenic differentiation during muscle regeneration
title_short Rbm24 displays dynamic functions required for myogenic differentiation during muscle regeneration
title_full Rbm24 displays dynamic functions required for myogenic differentiation during muscle regeneration
title_fullStr Rbm24 displays dynamic functions required for myogenic differentiation during muscle regeneration
title_full_unstemmed Rbm24 displays dynamic functions required for myogenic differentiation during muscle regeneration
title_sort rbm24 displays dynamic functions required for myogenic differentiation during muscle regeneration
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/7e2df0f3ea7e404ead019033bc8f3956
work_keys_str_mv AT raphaellegrifone rbm24displaysdynamicfunctionsrequiredformyogenicdifferentiationduringmuscleregeneration
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