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Regulation of miRNAs in human skeletal muscle following acute endurance exercise and short‐term endurance training
Author(s) -
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
Publication year - 2013
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2013.255695
Subject(s) - drosha , dicer , skeletal muscle , microrna , mitochondrial biogenesis , biology , endurance training , untranslated region , three prime untranslated region , microbiology and biotechnology , medicine , endocrinology , mitochondrion , messenger rna , genetics , gene , rna interference , rna
Key points• The discovery of microRNAs (miRNAs) has established new mechanisms that control health, but little is known about the regulation of skeletal muscle miRNAs in response to exercise. • This study investigated 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, and showed that 3 h following an acute exercise bout, Drosha , Dicer and Exportin‐5 , as well as miR‐1, ‐133a, ‐133‐b and miR‐181a were all increased, while miR‐9, ‐23a, ‐23b and ‐31 were decreased. • Short‐term training increased miR‐1 and miR‐29b, while miR‐31 remained decreased. • Negative correlations were observed between miR‐9 and HDAC4 protein, miR‐31 and HDAC4 protein and between miR‐31 and NRF1 protein, 3 h after 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 potentially involved in the regulation of skeletal muscle regeneration, gene transcription and mitochondrial biogenesis.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.