Multi-transcriptome analysis following an acute skeletal muscle growth stimulus yields tools for discerning global and MYC regulatory networks

Murach, Kevin A.; Liu, Zhengye; Jude, Baptiste; Figueiredo, Vandré Casagrande; Wen, Yan; Khadgi, Sabin; Lim, Seongkyun; Silva, Francielly Morena da; Greene, Nicholas P.; Lanner, Johanna T.; McCarthy, John J.; Vechetti, Ivan J.; Walden, Ferdinand von

doi:10.1016/j.jbc.2022.102515

Cited by 25 publications

(63 citation statements)

References 106 publications

(150 reference statements)

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“…We also identified Ankrd1 as a conserved upregulated transcription factor across species which was recently highlighted as the most upregulated gene in a myonuclear-specific transcriptome following synergist ablation. 71 This gene transcript is enriched in myotendinous junction myonuclei 70 and as a transcription factor commonly found in both cardiac and skeletal muscle, its transcriptional role in remodeling these tissues and specific muscle regions warrants further investigation.…”

Section: Discussionmentioning

confidence: 97%

“…This suggests that Myc plays an important role in the transcriptional regulation of hypertrophy induced by increased mechanical loading. Recent work from Murach et al 71 identified Myc as a myonuclei‐enriched hypertrophic gene. Inducible skeletal muscle‐specific overexpression of Myc identified a number of Myc targets including those involved in translation initiation, metabolism of RNA, ribosome, spliceosome, aminoacyl‐tRNA biosynthesis.…”

Section: Discussionmentioning

confidence: 99%

“…This suggests that Myc plays an important role in the transcriptional regulation of trophy induced by increased mechanical loading. Recent work from Murach et al 71…”

Section: Discussionmentioning

confidence: 99%

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Adaptation of the transcriptional response to resistance exercise over 4 weeks of daily training

et al. 2022

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We present the time course of change in the muscle transcriptome 1 h after the last exercise bout of a daily resistance training program lasting 2, 10, 20, or 30 days. Daily exercise in rat tibialis anterior muscles (5 sets of 10 repetitions over 20 min) induced progressive muscle growth that approached a new stable state after 30 days. The acute transcriptional response changed along with progressive adaptation of the muscle phenotype. For example, expression of type 2B myosin was silenced. Time courses recently synthesized from human exercise studies do not demonstrate so clearly the interplay between the acute exercise response and the longer‐term consequences of repeated exercise. We highlight classes of transcripts and transcription factors whose expression increases during the growth phase and declines again as the muscle adapts to a new daily pattern of activity and reduces its rate of growth. Myc appears to play a central role.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

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Adaptation of the transcriptional response to resistance exercise over 4 weeks of daily training

et al. 2022

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“…RNA extraction was performed using TRI reagent (Sigma-Aldrich, St. Louis, MO, United States) coupled with further columns-based processing using the Direct-zol Kit (Zymo Research, Irvine, CA, United States). RNA sequencing was performed by Novogene on a Illumina HiSeq using 150 bp paired-end sequencing ( Murach et al, 2022 ). The complete data set is publicly available at Gene Expression Omnibus with accession ID (GSE219100).…”

Section: Methodsmentioning

confidence: 99%

Extracellular vesicle characteristics and microRNA content in cerebral palsy and typically developed individuals at rest and in response to aerobic exercise

et al. 2022

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In this study, the properties of circulating extracellular vesicles (EVs) were examined in cerebral palsy (CP) and typically developed (TD) individuals at rest and after aerobic exercise, focusing on the size, concentration, and microRNA cargo of EVs. Nine adult individuals with CP performed a single exercise bout consisting of 45 min of Frame Running, and TD participants completed either 45 min of cycling (n = 10; TD EX) or were enrolled as controls with no exercise (n = 10; TD CON). Blood was drawn before and 30 min after exercise and analyzed for EV concentration, size, and microRNA content. The size of EVs was similar in CP vs. TD, and exercise had no effect. Individuals with CP had an overall lower concentration (∼25%, p < 0.05) of EVs. At baseline, let-7a, let-7b and let-7e were downregulated in individuals with CP compared to TD (p < 0.05), while miR-100 expression was higher, and miR-877 and miR-4433 lower in CP compared to TD after exercise (p < 0.05). Interestingly, miR-486 was upregulated ∼2-fold in the EVs of CP vs. TD both at baseline and after exercise. We then performed an in silico analysis of miR-486 targets and identified the satellite cell stemness factor Pax7 as a target of miR-486. C2C12 myoblasts were cultured with a miR-486 mimetic and RNA-sequencing was performed. Gene enrichment analysis revealed that several genes involved in sarcomerogenesis and extracellular matrix (ECM) were downregulated. Our data suggest that circulating miR-486 transported by EVs is elevated in individuals with CP and that miR-486 alters the transcriptome of myoblasts affecting both ECM- and sarcomerogenesis-related genes, providing a link to the skeletal muscle alterations observed in individuals with CP.

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“…Following denervation, myonuclear subgroups undergo transcriptional reprogramming and express a distinct signature that includes increased Runx1 and Gadd4 (Lin et al., 2022). Runx1 is enriched in myonuclei during loading‐induced hypertrophy (Murach et al., 2022), suggesting Runx1 expression during atrophy is a compensatory response. In response to a bout of endurance/resistance exercise in the absence of satellite cells, a population of ‘cryptic’ myonuclei arise that lack a clear identity (Wen et al., 2021).…”

Section: Introductionmentioning

confidence: 99%

The myonuclear domain in adult skeletal muscle fibres: past, present and future

Bagley

Denes

McCarthy

et al. 2023

The Journal of Physiology

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Most cells in the body are mononuclear whereas skeletal muscle fibres are uniquely multinuclear. The nuclei of muscle fibres (myonuclei) are usually situated peripherally which complicates the equitable distribution of gene products. Myonuclear abundance can also change under conditions such as hypertrophy and atrophy. Specialised zones in muscle fibres have different functions and thus distinct synthetic demands from myonuclei. The complex structure and regulatory requirements of multinuclear muscle cells understandably led to the hypothesis that myonuclei govern defined 'domains' to maintain homeostasis and facilitate adaptation. The purpose of this review is to provide historical context for the myonuclear domain and evaluate its veracity with respect to mRNA and protein distribution resulting from myonuclear transcription. We synthesise insights from past and current in vitro and in vivo genetically modified models for studying the myonuclear domain under dynamic conditions. We also cover the most contemporary knowledge on mRNA and protein transport in muscle cells. Insights from emerging technologies such as single myonuclear RNA-sequencing further inform our discussion of the myonuclear domain. We broadly conclude: (1) the myonuclear domain can be flexible during muscle fibre growth and atrophy, (2) the mechanisms and role of myonuclear loss and motility deserve further consideration, (3) mRNA in muscle is actively transported via microtubules and locally restricted, but proteins may travel far from a myonucleus of origin and (4) myonuclear transcriptional specialisation extends beyond the classic neuromuscular and myotendinous populations. A deeper understanding of the myonuclear domain in muscle may promote effective therapies for ageing and disease.

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Multi-transcriptome analysis following an acute skeletal muscle growth stimulus yields tools for discerning global and MYC regulatory networks

Cited by 25 publications

References 106 publications

Adaptation of the transcriptional response to resistance exercise over 4 weeks of daily training

Adaptation of the transcriptional response to resistance exercise over 4 weeks of daily training

Extracellular vesicle characteristics and microRNA content in cerebral palsy and typically developed individuals at rest and in response to aerobic exercise

The myonuclear domain in adult skeletal muscle fibres: past, present and future

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