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

Author

Listed:
  • Brenda Janice Sánchez

    (McGill University, 3655 Promenade Sir William Osler
    Rosalind & Morris Goodman Cancer Research Center, McGill University, 3655 Promenade Sir William Osler)

  • Anne-Marie K. Tremblay

    (McGill University, 3655 Promenade Sir William Osler
    Rosalind & Morris Goodman Cancer Research Center, McGill University, 3655 Promenade Sir William Osler)

  • Jean-Philippe Leduc-Gaudet

    (McGill University Health Centre Research Institute)

  • Derek T. Hall

    (McGill University, 3655 Promenade Sir William Osler
    Rosalind & Morris Goodman Cancer Research Center, McGill University, 3655 Promenade Sir William Osler)

  • Erzsebet Kovacs

    (Rosalind & Morris Goodman Cancer Research Center, McGill University, 3655 Promenade Sir William Osler)

  • Jennifer F. Ma

    (McGill University, 3655 Promenade Sir William Osler
    Rosalind & Morris Goodman Cancer Research Center, McGill University, 3655 Promenade Sir William Osler)

  • Souad Mubaid

    (McGill University, 3655 Promenade Sir William Osler
    Rosalind & Morris Goodman Cancer Research Center, McGill University, 3655 Promenade Sir William Osler)

  • Patricia L. Hallauer

    (McGill University)

  • Brittany L. Phillips

    (Emory University)

  • Katherine E. Vest

    (University of Cincinnati College of Medicine, 231 Albert Sabin Way)

  • Anita H. Corbett

    (Emory University)

  • Dimitris L. Kontoyiannis

    (Biomedical Sciences Research Centre “Alexander Fleming”, Institute of Fundamental Biomedical Research
    Department of Genetics, Development & Molecular Biology)

  • Sabah N. A. Hussain

    (McGill University Health Centre Research Institute)

  • Kenneth E. M. Hastings

    (McGill University)

  • Sergio Marco

    (McGill University, 3655 Promenade Sir William Osler
    Rosalind & Morris Goodman Cancer Research Center, McGill University, 3655 Promenade Sir William Osler)

  • Imed-Eddine Gallouzi

    (McGill University, 3655 Promenade Sir William Osler
    Rosalind & Morris Goodman Cancer Research Center, McGill University, 3655 Promenade Sir William Osler)

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.

Suggested Citation

  • 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 , 2019. "Depletion of HuR in murine skeletal muscle enhances exercise endurance and prevents cancer-induced muscle atrophy," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12186-6
    DOI: 10.1038/s41467-019-12186-6
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