SUMO system – a key regulator in sarcomere organization

Nayak, Arnab; Amrute-Nayak, Mamta

doi:10.1111/febs.15263

Cited by 10 publications

(7 citation statements)

References 101 publications

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“…Muscle fiber types are heterogeneous, displaying protein isoform-specific signatures that impart distinctive functionalities to meet diverse physiological demands ( Armstrong & Phelps, 1984 ; Bottinelli & Reggiani, 2000 ; Bottinelli, 2001 ; Schiaffino & Reggiani, 2011 ; Schiaffino et al, 2020 ). Composite muscle fiber profiles are a result of coordinated regulation of gene expression ( Firulli & Olson, 1997 ; Black & Olson, 1998 ; Majesky, 2007 ), co-integrated with protein isoform transitions facilitated by alternative splicing ( Smith et al, 1989 ; Guo et al, 2010 ; Kalsotra & Cooper, 2011 ; Nikonova et al, 2020 ), accompanied by post-translational modifications ( Anthony et al, 2002 ; Michele & Campbell, 2003 ; Wells et al, 2003 ; Nayak & Amrute-Nayak, 2020 ). The underlying molecular changes are initially regulated by the intrinsic developmental program ( Firulli & Olson, 1997 ; Kablar & Rudnicki, 2000 ), and later modulated by nerve stimulation, physiological demands, and pathophysiological conditions ( Hughes et al, 1993 ; Pette & Staron, 2001 ; Schiaffino et al, 2007 ; Pistoni et al, 2010 ).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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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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Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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“…Muscles develop to accommodate a heterogeneous composition of fiber-types with protein isoformspecific signatures that impart distinctive functionalities to meet diverse physiological demands (Armstrong and Phelps, 1984;Bottinelli, 2001;Bottinelli and Reggiani, 2000;Schiaffino and Reggiani, 2011;Schiaffino et al, 2020). Composite muscle fiber profiles are a result of coordinated regulation of gene expression (Black and Olson, 1998;Firulli and Olson, 1997;Majesky, 2007), co-integrated with protein isoform transitions facilitated by alternative splicing (Guo et al, 2010;Kalsotra and Cooper, 2011;Nikonova et al, 2020;Smith et al, 1989), accompanied by post-translational modifications (Anthony et al, 2002;Michele and Campbell, 2003;Nayak and Amrute-Nayak, 2020;Wells et al, 2003). The underlying molecular changes are initially regulated by the intrinsic developmental program (Firulli and Olson, 1997;Kablar and Rudnicki, 2000), and later modulated by nerve stimulation, physiological demands and patho-physiological conditions (Hughes et al, 1993;Pette and Staron, 2001;Pistoni et al, 2010;Schiaffino et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Rbfox1 is required for myofibril development and maintaining fiber-type specific isoform expression inDrosophilamuscles

Nikonova

Kamble

Mukherjee

et al. 2021

Preprint

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Protein isoform transitions confer distinct properties on muscle fibers and are regulated predominantly by differential transcription and alternative splicing. RNA-binding Fox protein 1 (Rbfox1) can affect both transcript levels and splicing, and is known to control skeletal muscle function. However, the detailed mechanisms by which Rbfox1 contributes to normal muscle development and physiology remain obscure. In this study, we report that Rbfox1 contributes to the generation of adult muscle diversity in Drosophila. Rbfox1 is differentially expressed in tubular and fibrillar muscle fiber types. RNAi knockdown of Rbfox1 leads to a loss of flight, climbing and jumping ability, as well as eclosion defects. Myofibers in knockdown muscle are frequently torn, and sarcomeres are hypercontracted. These defects arise from mis-regulation of fiber-type specific gene and splice isoform expression, notably loss of an IFM-specific isoform of Troponin-I that is critical for regulating myosin activity. We find that Rbfox1 influences mRNA transcript levels through 1) direct binding of 3'-UTRs of target transcripts as well as 2) through regulation of myogenic transcription factors, including Mef2, Exd and Salm. Moreover, Rbfox1 modulates splice isoform expression through 1) direct regulation of target splice events in structural genes and 2) regulation of the CELF-family RNA-binding protein Bruno1. Our data indicate that cross-regulatory interactions observed between FOX and CELF family RNA-binding proteins in vertebrates are conserved between their counterparts, Rbfox1 and Bruno1 in flies. Rbfox1 thus affects muscle development by regulation of both fiber-type specific gene and gene isoform expression dynamics of identity genes and structural proteins.

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“…These filaments are organized in a structure called sarcomere. SUMOylation has, in recent years, emerged as a key regulator in sarcomere organization [31]. It was shown that the level of mitochondrial-specific IMM lipid CL oscillates during the diurnal cycle in myotubes [32].…”

Section: Physiologic Situationmentioning

confidence: 99%

Mitochondria at Work: New Insights into Regulation and Dysregulation of Cellular Energy Supply and Metabolism

Schirrmacher¹

2020

Biomedicines

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Mitochondria are of great relevance to health, and their dysregulation is associated with major chronic diseases. Research on mitochondria—156 brand new publications from 2019 and 2020—have contributed to this review. Mitochondria have been fundamental for the evolution of complex organisms. As important and semi-autonomous organelles in cells, they can adapt their function to the needs of the respective organ. They can program their function to energy supply (e.g., to keep heart muscle cells going, life-long) or to metabolism (e.g., to support hepatocytes and liver function). The capacity of mitochondria to re-program between different options is important for all cell types that are capable of changing between a resting state and cell proliferation, such as stem cells and immune cells. Major chronic diseases are characterized by mitochondrial dysregulation. This will be exemplified by cardiovascular diseases, metabolic syndrome, neurodegenerative diseases, immune system disorders, and cancer. New strategies for intervention in chronic diseases will be presented. The tumor microenvironment can be considered a battlefield between cancer and immune defense, competing for energy supply and metabolism. Cancer cachexia is considered as a final stage of cancer progression. Nevertheless, the review will present an example of complete remission of cachexia via immune cell transfer. These findings should encourage studies along the lines of mitochondria, energy supply, and metabolism.

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SUMO system – a key regulator in sarcomere organization

Cited by 10 publications

References 101 publications

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

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

Rbfox1 is required for myofibril development and maintaining fiber-type specific isoform expression inDrosophilamuscles

Mitochondria at Work: New Insights into Regulation and Dysregulation of Cellular Energy Supply and Metabolism

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