期刊
NATURE COMMUNICATIONS
卷 10, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-019-12186-6
关键词
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资金
- CIHR operating grants [MOP-142399, MOP-89798]
- NSERC [RGPIN-2014-06035]
- Concejo Nacional de Ciencia y Tecnologia (CONACyT)
- Fonds de recherche du Quebec-Nature et technologies (FRQNT)
- Biochemistry department at McGill University
- CIHR/FRSQ training grant in cancer research of the McGill Integrated Cancer Research Training Program
- Canadian Institute of Health Research (CIHR)
- Chemical Biology Program at McGill University
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-1 alpha 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.
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