Depletion of HuR in murine skeletal muscle enhances exercise endurance and prevents cancer-induced muscle atrophy
| Autor: | Sergio Di Marco, Jean-Philippe Leduc-Gaudet, Jennifer F. Ma, Imed-Eddine Gallouzi, Erzsébet Nagy Kovács, Brittany L. Phillips, Anne-Marie K. Tremblay, Patricia L. Hallauer, Kenneth E. M. Hastings, Dimitris L. Kontoyiannis, Souad Mubaid, Derek T Hall, Brenda Janice Sanchez, Sabah N. A. Hussain, Katherine E. Vest, Anita H. Corbett |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Science Regulator General Physics and Astronomy Skeletal muscle Oxidative phosphorylation General Biochemistry Genetics and Molecular Biology Article Cell Line ELAV-Like Protein 1 03 medical and health sciences Mice 0302 clinical medicine Cell Line Tumor Neoplasms medicine Myocyte Animals Glycolysis Muscle Skeletal lcsh:Science Cancer Mice Knockout Messenger RNA Multidisciplinary Chemistry General Chemistry Immunohistochemistry Muscle atrophy Cell biology Muscular Atrophy 030104 developmental biology medicine.anatomical_structure Cross-Sectional Studies Gene Expression Regulation Cell culture lcsh:Q medicine.symptom 030217 neurology & neurosurgery |
| Zdroj: | Nature Communications, Vol 10, Iss 1, Pp 1-17 (2019) Nature Communications |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-019-12186-6 |
| Popis: | The master posttranscriptional regulator HuR promotes muscle fiber formation in cultured muscle cells. However, its impact on muscle physiology and function in vivo is still unclear. Here, we show that muscle-specific HuR knockout (muHuR-KO) mice have high exercise endurance that is associated with enhanced oxygen consumption and carbon dioxide production. muHuR-KO mice exhibit a significant increase in the proportion of oxidative type I fibers in several skeletal muscles. HuR mediates these effects by collaborating with the mRNA decay factor KSRP to destabilize the PGC-1α mRNA. The type I fiber-enriched phenotype of muHuR-KO mice protects against cancer cachexia-induced muscle loss. Therefore, our study uncovers that under normal conditions HuR modulates muscle fiber type specification by promoting the formation of glycolytic type II fibers. We also provide a proof-of-principle that HuR expression can be targeted therapeutically in skeletal muscles to combat cancer-induced muscle wasting. HuR is an RNA-binding protein that regulates myotube differentiation in vitro. Here, the authors show that the muscle-specific ablation of HuR in mice leads to enhanced endurance capacity and an increase in oxidative fibres by destabilising PGC1α-mRNA, and show that the mice are protected against cancer cachexia |
| Databáze: | OpenAIRE |
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