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 Eddine Gallouzi

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

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 (US)
JournalNature Communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019
Externally publishedYes

Bibliographical note

Generated from Scopus record by KAUST IRTS on 2022-09-13

ASJC Scopus subject areas

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

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