Regulation of Ribosome Biogenesis During Skeletal Muscle Hypertrophy

Kim, Hyo Gun; Guo, Bin; Nader, Gustavo A.

doi:10.1249/jes.0000000000000179

Cited by 23 publications

(17 citation statements)

References 46 publications

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“…Ribosomes are the molecular factories responsible for protein synthesis, which is a key process in the long-term adaptive response to exercise in skeletal muscle (Figueiredo, 2019a;. Ribosome biogenesis is stimulated by muscle loading (Figueiredo & McCarthy, 2019b; Kim et al, 2019;von Walden, 2019b), and the magnitude of de novo synthesis of ribosomes is proportional to the amount of load-induced adult muscle hypertrophy in both rodents (Nakada et al, 2016) and humans (Figueiredo et al, 2015;Stec et al, 2016;Hammarstrom et al, 2020). Mechanical loading rapidly induces RNA Polymerase I (Pol I) transcription of ribosomal DNA (rDNA), as assessed by 45S pre-rRNA transcription levels and accumulation of rRNA (von Walden et al, 2012b;Kirby et al, 2016;Figueiredo et al, 2019b).…”

Section: Introductionmentioning

confidence: 99%

Genetic and Epigenetic Regulation of Skeletal Muscle Ribosome Biogenesis with Exercise

Figueiredo

Wen

Alkner

et al. 2020

Preprint

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Ribosomes are the macromolecular engines of protein synthesis. Skeletal muscle ribosome biogenesis is stimulated by exercise, but the contribution of ribosomal DNA (rDNA) copy number and methylation to exercise-induced rDNA transcription is unclear. To investigate the genetic and epigenetic regulation of ribosome biogenesis with exercise, a time course of skeletal muscle biopsies was obtained from 30 participants (18 men and 12 women; 31 ±8 yrs, 25 ±4 kg/m2) at rest and 30 min, 3h, 8h, and 24h after acute endurance (n=10, 45 min cycling, 70% VO2max) or resistance exercise (n=10, 4 x 7 x 2 exercises); 10 control participants underwent biopsies without exercise. rDNA transcription and dosage were assessed using qPCR and whole genome sequencing. rDNA promoter methylation was investigated using massARRAY EpiTYPER, and global rDNA CpG methylation was assessed using reduced-representation bisulfite sequencing. Ribosome biogenesis and MYC transcription were associated with resistance but not endurance exercise, indicating preferential up-regulation during hypertrophic processes. With resistance exercise, ribosome biogenesis was associated with rDNA gene dosage as well as epigenetic changes in enhancer and non-canonical MYC-associated areas in rDNA, but not the promoter. A mouse model of in vivo metabolic RNA labeling and genetic myonuclear fluorescent labeling validated the effects of an acute hypertrophic stimulus on ribosome biogenesis and Myc transcription, and corroborated rDNA enhancer and Myc-associated methylation alterations specifically in myonuclei. This study provides the first information on skeletal muscle genetic and rDNA gene-wide epigenetic regulation of ribosome biogenesis in response to exercise, revealing novel roles for rDNA dosage and CpG methylation.GRAPHICAL ABSTRACT

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Section: Introductionmentioning

confidence: 99%

Genetic and Epigenetic Regulation of Skeletal Muscle Ribosome Biogenesis with Exercise

Figueiredo

Wen

Alkner

et al. 2020

Preprint

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“…It was noted that despite the increased rRNA after an acute RE, we could not detect a concomitant change in total RNA expression. Although the mechanism of discrepancy between the change in rRNA content and total RNA content is unclear, one possible explanation is that an difficulty to precisely measure small change in the rRNA, since the total RNA contains other RNAs such as small RNA, tRNA, and mRNA (Figueiredo and McCarthy, 2019).…”

Section: Discussionmentioning

confidence: 99%

“…A previous study observed that resting intracellular ribosomal content is highly correlated to the MPS (Millward et al, 1973). Moreover, recent evidence suggests that the capacity of ribosome biogenesis is relevant to the response of load-induced skeletal muscle hypertrophy (von Walden et al, 2012;Kirby et al, 2015;Figueiredo and McCarthy, 2019).…”

Section: Introductionmentioning

confidence: 95%

Response of Resistance Exercise-Induced Muscle Protein Synthesis and Skeletal Muscle Hypertrophy Are Not Enhanced After Disuse Muscle Atrophy in Rat

et al. 2020

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Skeletal muscle disuse rapidly decreases muscle mass. Resistance training (RT) is believed as the most effective way to gain muscle mass via an increase in mTORC1 activity and muscle protein synthesis (MPS). However, it remains unclear whether muscle atrophy by disuse alters the mTORC1 activation and MPS response to an acute resistance exercise (RE) and chronic RT-mediated skeletal muscle hypertrophy. This study investigated the influence of disuse muscle atrophy on the response of mTORC1 activation and MPS to an acute RE. We also evaluated whether disuse muscle atrophy affects the response of RT-induced muscle mass gain. Thirty male Sprague-Dawley rats were randomly divided into control (CON) or hindlimb suspension (HS) groups. A 14-day HS via the tail was used as the model for gastrocnemius muscle disuse in the HS group. Unilateral lower limb muscle contraction using by percutaneous electrical stimulation was used to mimic the stimuli of RE. Ten bouts of RE were performed in 3-week as chronic RT. Our results showed that MPS and mTORC1 activity was unchanged after HS at basal state. However, the ribosomal RNA (rRNA) level was reduced in HS rats compared to that in CON rats at basal state. MPS and rRNA increased in both HS and CON rats in response to acute RE to the same extent. However, the level of mTORC1 activation in response to an acute RE was significantly higher in HS than that in the CON group at 12 h after exercise, even though no difference was observed at 3 h after exercise. The 10-bout RT significantly increased gastrocnemius muscle mass in both CON and HS rats. The response of muscle hypertrophy did not differ between the groups. Therefore, MPS in response to acute RE and muscle hypertrophy in response to chronic RT were unaltered after disuse muscle atrophy.

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“…Resistance and endurance training increase skeletal muscle ribosome biogenesis and mitochondrial biogenesis, respectively. Mitochondrial biogenesis increases aerobic capacity ( Costill et al, 1976 ; Burgomaster et al, 2008 ; Yeo et al, 2008 ; Murias et al, 2011 ; Cochran et al, 2014 ; Vigelso et al, 2014 ), and ribosome biogenesis has been associated with skeletal muscle hypertrophy [reviewed in ( Chaillou et al, 2014 ; Wen et al, 2016 ; Mcglory et al, 2017 ; Bamman et al, 2018 ; Roberts et al, 2018a ; Figueiredo and Mccarthy, 2019 ; Kim et al, 2019 )]. It is generally believed that skeletal muscle adaptations to exercise are highly specific.…”

Section: Introductionmentioning

confidence: 99%

Skeletal Muscle Ribosome and Mitochondrial Biogenesis in Response to Different Exercise Training Modalities

et al. 2021

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Skeletal muscle adaptations to resistance and endurance training include increased ribosome and mitochondrial biogenesis, respectively. Such adaptations are believed to contribute to the notable increases in hypertrophy and aerobic capacity observed with each exercise mode. Data from multiple studies suggest the existence of a competition between ribosome and mitochondrial biogenesis, in which the first adaptation is prioritized with resistance training while the latter is prioritized with endurance training. In addition, reports have shown an interference effect when both exercise modes are performed concurrently. This prioritization/interference may be due to the interplay between the 5’ AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin complex 1 (mTORC1) signaling cascades and/or the high skeletal muscle energy requirements for the synthesis and maintenance of cellular organelles. Negative associations between ribosomal DNA and mitochondrial DNA copy number in human blood cells also provide evidence of potential competition in skeletal muscle. However, several lines of evidence suggest that ribosome and mitochondrial biogenesis can occur simultaneously in response to different types of exercise and that the AMPK-mTORC1 interaction is more complex than initially thought. The purpose of this review is to provide in-depth discussions of these topics. We discuss whether a curious competition between mitochondrial and ribosome biogenesis exists and show the available evidence both in favor and against it. Finally, we provide future research avenues in this area of exercise physiology.

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Regulation of Ribosome Biogenesis During Skeletal Muscle Hypertrophy

Abstract: An increase in ribosomal capacity is a hallmark of the hypertrophying muscle. We review evidence demonstrating that transcription of ribosomal RNA genes is necessary for the increase in ribosomal capacity, and this is critical for muscle growth in human and animal models of hypertrophy.

Cited by 23 publications

References 46 publications

Genetic and Epigenetic Regulation of Skeletal Muscle Ribosome Biogenesis with Exercise

Genetic and Epigenetic Regulation of Skeletal Muscle Ribosome Biogenesis with Exercise

Response of Resistance Exercise-Induced Muscle Protein Synthesis and Skeletal Muscle Hypertrophy Are Not Enhanced After Disuse Muscle Atrophy in Rat

Skeletal Muscle Ribosome and Mitochondrial Biogenesis in Response to Different Exercise Training Modalities

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