MicroRNA-494 regulates mitochondrial biogenesis in skeletal muscle through mitochondrial transcription factor A and Forkhead box j3

MicroRNAs (miRNAs) are important posttranscriptional regulators of various biological pathways. In this study, we focused on the role of miRNAs during mitochondrial biogenesis in skeletal muscle. The expression of miR-494 was markedly decreased in murine myoblast C₂C₁₂ cells during myogenic differen...

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Veröffentlicht in:American journal of physiology: endocrinology and metabolism 2012-12, Vol.303 (12), p.E1419-E1427
Hauptverfasser: Yamamoto, Hirotaka, Morino, Katsutaro, Nishio, Yoshihiko, Ugi, Satoshi, Yoshizaki, Takeshi, Kashiwagi, Atsunori, Maegawa, Hiroshi
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container_end_page E1427
container_issue 12
container_start_page E1419
container_title American journal of physiology: endocrinology and metabolism
container_volume 303
creator Yamamoto, Hirotaka
Morino, Katsutaro
Nishio, Yoshihiko
Ugi, Satoshi
Yoshizaki, Takeshi
Kashiwagi, Atsunori
Maegawa, Hiroshi
description MicroRNAs (miRNAs) are important posttranscriptional regulators of various biological pathways. In this study, we focused on the role of miRNAs during mitochondrial biogenesis in skeletal muscle. The expression of miR-494 was markedly decreased in murine myoblast C₂C₁₂ cells during myogenic differentiation, accompanied by an increase in mtDNA. Furthermore, the expression of predicted target genes for miR-494, including mitochondrial transcription factor A (mtTFA) and Forkhead box j3 (Foxj3), was posttranscriptionally increased during myogenic differentiation. Knockdown of miR-494 resulted in increased mitochondrial content and upregulation of mtTFA and Foxj3 at the protein level. A 3'-untranslated region reporter assay revealed that miR-494 knockdown directly upregulated the luciferase activity of mtTFA and Foxj3. All of these observations were reversed by overexpression of miR-494. Furthermore, the miR-494 content significantly decreased after endurance exercise in C57BL/6J mice, accompanied by an increase in expression of mtTFA and Foxj3 proteins. These results suggest that miR-494 regulates mitochondrial biogenesis by downregulating mtTFA and Foxj3 during myocyte differentiation and skeletal muscle adaptation to physical exercise.
doi_str_mv 10.1152/ajpendo.00097.2012
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subjects Animals
Biosynthesis
Cell Differentiation
Cell Line
Cells
DNA, Mitochondrial - metabolism
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Down-Regulation
Exercise
Genes, Reporter
Male
Mice
Mice, Inbred C57BL
MicroRNAs - antagonists & inhibitors
MicroRNAs - genetics
MicroRNAs - metabolism
Mitochondria, Muscle - metabolism
Mitochondrial DNA
Mitochondrial Proteins - genetics
Mitochondrial Proteins - metabolism
Mitochondrial Turnover
Motor Activity
Muscle, Skeletal - metabolism
Musculoskeletal system
Myoblasts - cytology
Myoblasts - metabolism
Oligoribonucleotides, Antisense - metabolism
Proteins
Random Allocation
Recombinant Proteins - metabolism
RNA, Messenger - metabolism
Rodents
Transcription Factors - genetics
Transcription Factors - metabolism
Up-Regulation
title MicroRNA-494 regulates mitochondrial biogenesis in skeletal muscle through mitochondrial transcription factor A and Forkhead box j3
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