Depletion of HuR in murine skeletal muscle enhances exercise endurance and prevents cancer-induced muscle atrophy

Brenda Janice Sánchez, Anne Marie K. Tremblay, Jean Philippe Leduc-Gaudet, Derek T. Hall, Erzsebet Kovacs, Jennifer F. Ma, Souad Mubaid, Patricia L. Hallauer, Brittany L. Phillips, Katherine E. Vest, Anita H. Corbett, Dimitris L. Kontoyiannis, Sabah N.A. Hussain, Kenneth E.M. Hastings, Sergio Di Marco, Imed Gallouzi

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Abstract

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.

Original languageEnglish
Number of pages1
JournalNature communications
Volume10
Issue number1
DOIs
Publication statusPublished - 13 Sep 2019

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ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Janice Sánchez, B., Tremblay, A. M. K., Leduc-Gaudet, J. P., Hall, D. T., Kovacs, E., Ma, J. F., Mubaid, S., Hallauer, P. L., Phillips, B. L., Vest, K. E., Corbett, A. H., Kontoyiannis, D. L., Hussain, S. N. A., Hastings, K. E. M., Di Marco, S., & Gallouzi, I. (2019). Depletion of HuR in murine skeletal muscle enhances exercise endurance and prevents cancer-induced muscle atrophy. Nature communications, 10(1). https://doi.org/10.1038/s41467-019-12186-6