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 |
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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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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. 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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. 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Morino, Katsutaro ; Nishio, Yoshihiko ; Ugi, Satoshi ; Yoshizaki, Takeshi ; Kashiwagi, Atsunori ; Maegawa, Hiroshi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c397t-d907c37ea3d6826e2387366ec30dfd82e1b13f33362ff02ceafbc7f7a7be82463</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>Biosynthesis</topic><topic>Cell Differentiation</topic><topic>Cell Line</topic><topic>Cells</topic><topic>DNA, Mitochondrial - metabolism</topic><topic>DNA-Binding Proteins - genetics</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Down-Regulation</topic><topic>Exercise</topic><topic>Genes, Reporter</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>MicroRNAs - antagonists & inhibitors</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - metabolism</topic><topic>Mitochondria, Muscle - metabolism</topic><topic>Mitochondrial DNA</topic><topic>Mitochondrial Proteins - genetics</topic><topic>Mitochondrial Proteins - metabolism</topic><topic>Mitochondrial Turnover</topic><topic>Motor Activity</topic><topic>Muscle, Skeletal - metabolism</topic><topic>Musculoskeletal system</topic><topic>Myoblasts - cytology</topic><topic>Myoblasts - metabolism</topic><topic>Oligoribonucleotides, Antisense - metabolism</topic><topic>Proteins</topic><topic>Random Allocation</topic><topic>Recombinant Proteins - metabolism</topic><topic>RNA, Messenger - metabolism</topic><topic>Rodents</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - metabolism</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yamamoto, Hirotaka</creatorcontrib><creatorcontrib>Morino, Katsutaro</creatorcontrib><creatorcontrib>Nishio, Yoshihiko</creatorcontrib><creatorcontrib>Ugi, Satoshi</creatorcontrib><creatorcontrib>Yoshizaki, Takeshi</creatorcontrib><creatorcontrib>Kashiwagi, Atsunori</creatorcontrib><creatorcontrib>Maegawa, Hiroshi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Physical Education Index</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>MEDLINE - Academic</collection><jtitle>American journal of physiology: endocrinology and metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yamamoto, Hirotaka</au><au>Morino, Katsutaro</au><au>Nishio, Yoshihiko</au><au>Ugi, Satoshi</au><au>Yoshizaki, Takeshi</au><au>Kashiwagi, Atsunori</au><au>Maegawa, Hiroshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MicroRNA-494 regulates mitochondrial biogenesis in skeletal muscle through mitochondrial transcription factor A and Forkhead box j3</atitle><jtitle>American journal of physiology: endocrinology and metabolism</jtitle><addtitle>Am J Physiol Endocrinol Metab</addtitle><date>2012-12-15</date><risdate>2012</risdate><volume>303</volume><issue>12</issue><spage>E1419</spage><epage>E1427</epage><pages>E1419-E1427</pages><issn>0193-1849</issn><eissn>1522-1555</eissn><coden>AJPMD9</coden><abstract>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.</abstract><cop>United States</cop><pub>American Physiological Society</pub><pmid>23047984</pmid><doi>10.1152/ajpendo.00097.2012</doi></addata></record> |
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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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