Regulation of miRNAs in human skeletal muscle following acute endurance exercise and short-term endurance training

Aaron P. Russell, Severine Lamon, Hanneke Boon, Shogo Wada, Isabelle Güller, Erin L. Brown, Alexander V. Chibalin, Juleen R. Zierath, Rod J. Snow, Nigel Stepto, Glenn D. Wadley, Takayuki Akimoto

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

The identification of microRNAs (miRNAs) has established new mechanisms that control skeletal muscle adaptation to exercise. The present study investigated the mRNA regulation of components of the miRNA biogenesis pathway (Drosha, Dicer and Exportin-5), muscle enriched miRNAs, (miR-1, -133a, -133b and -206), and several miRNAs dysregulated in muscle myopathies (miR-9, -23, -29, -31 and -181). Measurements were made in muscle biopsies from nine healthy untrained males at rest, 3 h following an acute bout of moderate-intensity endurance cycling and following 10 days of endurance training. Bioinformatics analysis was used to predict potential miRNA targets. In the 3 h period following the acute exercise bout, Drosha, Dicer and Exportin-5, as well as miR-1, -133a, -133-b and -181a were all increased. In contrast miR-9, -23a, -23b and -31 were decreased. Short-term training increased miR-1 and -29b, while miR-31 remained decreased. Negative correlations were observed between miR-9 and HDAC4 protein (r=-0.71; P= 0.04), miR-31 and HDAC4 protein (r =-0.87; P= 0.026) and miR-31 and NRF1 protein (r =-0.77; P= 0.01) 3 h following exercise. miR-31 binding to the HDAC4 and NRF1 3′ untranslated region (UTR) reduced luciferase reporter activity. Exercise rapidly and transiently regulates several miRNA species in muscle. Several of these miRNAs may be involved in the regulation of skeletal muscle regeneration, gene transcription and mitochondrial biogenesis. Identifying endurance exercise-mediated stress signals regulating skeletal muscle miRNAs, as well as validating their targets and regulatory pathways post exercise, will advance our understanding of their potential role/s in human health.

Original languageEnglish
Pages (from-to)4637-4653
Number of pages17
JournalJournal of Physiology
Volume591
Issue number18
DOIs
Publication statusPublished - 2013 Sep
Externally publishedYes

Fingerprint

MicroRNAs
Skeletal Muscle
Exercise
Karyopherins
Muscles
Proteins
3' Untranslated Regions
Organelle Biogenesis
Muscular Diseases
Computational Biology
Luciferases
Regeneration
Biopsy
Messenger RNA
Health
Genes

ASJC Scopus subject areas

  • Physiology

Cite this

Regulation of miRNAs in human skeletal muscle following acute endurance exercise and short-term endurance training. / Russell, Aaron P.; Lamon, Severine; Boon, Hanneke; Wada, Shogo; Güller, Isabelle; Brown, Erin L.; Chibalin, Alexander V.; Zierath, Juleen R.; Snow, Rod J.; Stepto, Nigel; Wadley, Glenn D.; Akimoto, Takayuki.

In: Journal of Physiology, Vol. 591, No. 18, 09.2013, p. 4637-4653.

Research output: Contribution to journalArticle

Russell, AP, Lamon, S, Boon, H, Wada, S, Güller, I, Brown, EL, Chibalin, AV, Zierath, JR, Snow, RJ, Stepto, N, Wadley, GD & Akimoto, T 2013, 'Regulation of miRNAs in human skeletal muscle following acute endurance exercise and short-term endurance training', Journal of Physiology, vol. 591, no. 18, pp. 4637-4653. https://doi.org/10.1113/jphysiol.2013.255695
Russell, Aaron P. ; Lamon, Severine ; Boon, Hanneke ; Wada, Shogo ; Güller, Isabelle ; Brown, Erin L. ; Chibalin, Alexander V. ; Zierath, Juleen R. ; Snow, Rod J. ; Stepto, Nigel ; Wadley, Glenn D. ; Akimoto, Takayuki. / Regulation of miRNAs in human skeletal muscle following acute endurance exercise and short-term endurance training. In: Journal of Physiology. 2013 ; Vol. 591, No. 18. pp. 4637-4653.
@article{8ea3ab23b3db407d8fe7d3d9c2181978,
title = "Regulation of miRNAs in human skeletal muscle following acute endurance exercise and short-term endurance training",
abstract = "The identification of microRNAs (miRNAs) has established new mechanisms that control skeletal muscle adaptation to exercise. The present study investigated the mRNA regulation of components of the miRNA biogenesis pathway (Drosha, Dicer and Exportin-5), muscle enriched miRNAs, (miR-1, -133a, -133b and -206), and several miRNAs dysregulated in muscle myopathies (miR-9, -23, -29, -31 and -181). Measurements were made in muscle biopsies from nine healthy untrained males at rest, 3 h following an acute bout of moderate-intensity endurance cycling and following 10 days of endurance training. Bioinformatics analysis was used to predict potential miRNA targets. In the 3 h period following the acute exercise bout, Drosha, Dicer and Exportin-5, as well as miR-1, -133a, -133-b and -181a were all increased. In contrast miR-9, -23a, -23b and -31 were decreased. Short-term training increased miR-1 and -29b, while miR-31 remained decreased. Negative correlations were observed between miR-9 and HDAC4 protein (r=-0.71; P= 0.04), miR-31 and HDAC4 protein (r =-0.87; P= 0.026) and miR-31 and NRF1 protein (r =-0.77; P= 0.01) 3 h following exercise. miR-31 binding to the HDAC4 and NRF1 3′ untranslated region (UTR) reduced luciferase reporter activity. Exercise rapidly and transiently regulates several miRNA species in muscle. Several of these miRNAs may be involved in the regulation of skeletal muscle regeneration, gene transcription and mitochondrial biogenesis. Identifying endurance exercise-mediated stress signals regulating skeletal muscle miRNAs, as well as validating their targets and regulatory pathways post exercise, will advance our understanding of their potential role/s in human health.",
author = "Russell, {Aaron P.} and Severine Lamon and Hanneke Boon and Shogo Wada and Isabelle G{\"u}ller and Brown, {Erin L.} and Chibalin, {Alexander V.} and Zierath, {Juleen R.} and Snow, {Rod J.} and Nigel Stepto and Wadley, {Glenn D.} and Takayuki Akimoto",
year = "2013",
month = "9",
doi = "10.1113/jphysiol.2013.255695",
language = "English",
volume = "591",
pages = "4637--4653",
journal = "Journal of Physiology",
issn = "0022-3751",
publisher = "Wiley-Blackwell",
number = "18",

}

TY - JOUR

T1 - Regulation of miRNAs in human skeletal muscle following acute endurance exercise and short-term endurance training

AU - Russell, Aaron P.

AU - Lamon, Severine

AU - Boon, Hanneke

AU - Wada, Shogo

AU - Güller, Isabelle

AU - Brown, Erin L.

AU - Chibalin, Alexander V.

AU - Zierath, Juleen R.

AU - Snow, Rod J.

AU - Stepto, Nigel

AU - Wadley, Glenn D.

AU - Akimoto, Takayuki

PY - 2013/9

Y1 - 2013/9

N2 - The identification of microRNAs (miRNAs) has established new mechanisms that control skeletal muscle adaptation to exercise. The present study investigated the mRNA regulation of components of the miRNA biogenesis pathway (Drosha, Dicer and Exportin-5), muscle enriched miRNAs, (miR-1, -133a, -133b and -206), and several miRNAs dysregulated in muscle myopathies (miR-9, -23, -29, -31 and -181). Measurements were made in muscle biopsies from nine healthy untrained males at rest, 3 h following an acute bout of moderate-intensity endurance cycling and following 10 days of endurance training. Bioinformatics analysis was used to predict potential miRNA targets. In the 3 h period following the acute exercise bout, Drosha, Dicer and Exportin-5, as well as miR-1, -133a, -133-b and -181a were all increased. In contrast miR-9, -23a, -23b and -31 were decreased. Short-term training increased miR-1 and -29b, while miR-31 remained decreased. Negative correlations were observed between miR-9 and HDAC4 protein (r=-0.71; P= 0.04), miR-31 and HDAC4 protein (r =-0.87; P= 0.026) and miR-31 and NRF1 protein (r =-0.77; P= 0.01) 3 h following exercise. miR-31 binding to the HDAC4 and NRF1 3′ untranslated region (UTR) reduced luciferase reporter activity. Exercise rapidly and transiently regulates several miRNA species in muscle. Several of these miRNAs may be involved in the regulation of skeletal muscle regeneration, gene transcription and mitochondrial biogenesis. Identifying endurance exercise-mediated stress signals regulating skeletal muscle miRNAs, as well as validating their targets and regulatory pathways post exercise, will advance our understanding of their potential role/s in human health.

AB - The identification of microRNAs (miRNAs) has established new mechanisms that control skeletal muscle adaptation to exercise. The present study investigated the mRNA regulation of components of the miRNA biogenesis pathway (Drosha, Dicer and Exportin-5), muscle enriched miRNAs, (miR-1, -133a, -133b and -206), and several miRNAs dysregulated in muscle myopathies (miR-9, -23, -29, -31 and -181). Measurements were made in muscle biopsies from nine healthy untrained males at rest, 3 h following an acute bout of moderate-intensity endurance cycling and following 10 days of endurance training. Bioinformatics analysis was used to predict potential miRNA targets. In the 3 h period following the acute exercise bout, Drosha, Dicer and Exportin-5, as well as miR-1, -133a, -133-b and -181a were all increased. In contrast miR-9, -23a, -23b and -31 were decreased. Short-term training increased miR-1 and -29b, while miR-31 remained decreased. Negative correlations were observed between miR-9 and HDAC4 protein (r=-0.71; P= 0.04), miR-31 and HDAC4 protein (r =-0.87; P= 0.026) and miR-31 and NRF1 protein (r =-0.77; P= 0.01) 3 h following exercise. miR-31 binding to the HDAC4 and NRF1 3′ untranslated region (UTR) reduced luciferase reporter activity. Exercise rapidly and transiently regulates several miRNA species in muscle. Several of these miRNAs may be involved in the regulation of skeletal muscle regeneration, gene transcription and mitochondrial biogenesis. Identifying endurance exercise-mediated stress signals regulating skeletal muscle miRNAs, as well as validating their targets and regulatory pathways post exercise, will advance our understanding of their potential role/s in human health.

UR - http://www.scopus.com/inward/record.url?scp=84884286848&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84884286848&partnerID=8YFLogxK

U2 - 10.1113/jphysiol.2013.255695

DO - 10.1113/jphysiol.2013.255695

M3 - Article

VL - 591

SP - 4637

EP - 4653

JO - Journal of Physiology

JF - Journal of Physiology

SN - 0022-3751

IS - 18

ER -