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Rbfox1 is required for myofibril development and maintaining fiber type–specific isoform expression in Drosophila muscles

Protein isoform transitions confer muscle fibers with distinct properties and are regulated by differential transcription and alternative splicing. RNA-binding Fox protein 1 (Rbfox1) can affect both transcript levels and splicing, and is known to contribute to normal muscle development and physiolog...

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Autores principales: Nikonova, Elena, Mukherjee, Amartya, Kamble, Ketaki, Barz, Christiane, Nongthomba, Upendra, Spletter, Maria L
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Life Science Alliance LLC 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8742874/
https://www.ncbi.nlm.nih.gov/pubmed/34996845
http://dx.doi.org/10.26508/lsa.202101342
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author Nikonova, Elena
Mukherjee, Amartya
Kamble, Ketaki
Barz, Christiane
Nongthomba, Upendra
Spletter, Maria L
author_facet Nikonova, Elena
Mukherjee, Amartya
Kamble, Ketaki
Barz, Christiane
Nongthomba, Upendra
Spletter, Maria L
author_sort Nikonova, Elena
collection PubMed
description Protein isoform transitions confer muscle fibers with distinct properties and are regulated by differential transcription and alternative splicing. RNA-binding Fox protein 1 (Rbfox1) can affect both transcript levels and splicing, and is known to contribute to normal muscle development and physiology in vertebrates, although the detailed mechanisms remain obscure. In this study, we report that Rbfox1 contributes to the generation of adult muscle diversity in Drosophila. Rbfox1 is differentially expressed among muscle fiber types, and RNAi knockdown causes a hypercontraction phenotype that leads to behavioral and eclosion defects. Misregulation of fiber type–specific gene and splice isoform expression, notably loss of an indirect flight muscle–specific isoform of Troponin-I that is critical for regulating myosin activity, leads to structural defects. We further show that Rbfox1 directly binds the 3′-UTR of target transcripts, regulates the expression level of myogenic transcription factors myocyte enhancer factor 2 and Salm, and both modulates expression of and genetically interacts with the CELF family RNA-binding protein Bruno1 (Bru1). Rbfox1 and Bru1 co-regulate fiber type–specific alternative splicing of structural genes, indicating that regulatory interactions between FOX and CELF family RNA-binding proteins are conserved in fly muscle. Rbfox1 thus affects muscle development by regulating fiber type–specific splicing and expression dynamics of identity genes and structural proteins.
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spelling pubmed-87428742022-01-25 Rbfox1 is required for myofibril development and maintaining fiber type–specific isoform expression in Drosophila muscles Nikonova, Elena Mukherjee, Amartya Kamble, Ketaki Barz, Christiane Nongthomba, Upendra Spletter, Maria L Life Sci Alliance Research Articles Protein isoform transitions confer muscle fibers with distinct properties and are regulated by differential transcription and alternative splicing. RNA-binding Fox protein 1 (Rbfox1) can affect both transcript levels and splicing, and is known to contribute to normal muscle development and physiology in vertebrates, although the detailed mechanisms remain obscure. In this study, we report that Rbfox1 contributes to the generation of adult muscle diversity in Drosophila. Rbfox1 is differentially expressed among muscle fiber types, and RNAi knockdown causes a hypercontraction phenotype that leads to behavioral and eclosion defects. Misregulation of fiber type–specific gene and splice isoform expression, notably loss of an indirect flight muscle–specific isoform of Troponin-I that is critical for regulating myosin activity, leads to structural defects. We further show that Rbfox1 directly binds the 3′-UTR of target transcripts, regulates the expression level of myogenic transcription factors myocyte enhancer factor 2 and Salm, and both modulates expression of and genetically interacts with the CELF family RNA-binding protein Bruno1 (Bru1). Rbfox1 and Bru1 co-regulate fiber type–specific alternative splicing of structural genes, indicating that regulatory interactions between FOX and CELF family RNA-binding proteins are conserved in fly muscle. Rbfox1 thus affects muscle development by regulating fiber type–specific splicing and expression dynamics of identity genes and structural proteins. Life Science Alliance LLC 2022-01-07 /pmc/articles/PMC8742874/ /pubmed/34996845 http://dx.doi.org/10.26508/lsa.202101342 Text en © 2022 Nikonova et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Articles
Nikonova, Elena
Mukherjee, Amartya
Kamble, Ketaki
Barz, Christiane
Nongthomba, Upendra
Spletter, Maria L
Rbfox1 is required for myofibril development and maintaining fiber type–specific isoform expression in Drosophila muscles
title Rbfox1 is required for myofibril development and maintaining fiber type–specific isoform expression in Drosophila muscles
title_full Rbfox1 is required for myofibril development and maintaining fiber type–specific isoform expression in Drosophila muscles
title_fullStr Rbfox1 is required for myofibril development and maintaining fiber type–specific isoform expression in Drosophila muscles
title_full_unstemmed Rbfox1 is required for myofibril development and maintaining fiber type–specific isoform expression in Drosophila muscles
title_short Rbfox1 is required for myofibril development and maintaining fiber type–specific isoform expression in Drosophila muscles
title_sort rbfox1 is required for myofibril development and maintaining fiber type–specific isoform expression in drosophila muscles
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8742874/
https://www.ncbi.nlm.nih.gov/pubmed/34996845
http://dx.doi.org/10.26508/lsa.202101342
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