Molecular Transducers of Human Skeletal Muscle Remodeling under Different Loading States Academic Article uri icon

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abstract

  • Loading of skeletal muscle changes the tissue phenotype reflecting altered metabolic and functional demands. In humans, heterogeneous adaptation to loading complicates the identification of the underpinning molecular regulators. A within-person differential loading and analysis strategy reduces heterogeneity for changes in muscle mass by ∼40% and uses a genome-wide transcriptome method that models each mRNA from coding exons and 3' and 5' untranslated regions (UTRs). Our strategy detects ∼3-4 times more regulated genes than similarly sized studies, including substantial UTR-selective regulation undetected by other methods. We discover a core of 141 genes correlated to muscle growth, which we validate from newly analyzed independent samples (n = 100). Further validating these identified genes via RNAi in primary muscle cells, we demonstrate that members of the core genes were regulators of protein synthesis. Using proteome-constrained networks and pathway analysis reveals notable relationships with the molecular characteristics of human muscle aging and insulin sensitivity, as well as potential drug therapies.

authors

  • Stokes, Tanner
  • Timmons, James A
  • Crossland, Hannah
  • Tripp, Thomas R
  • Murphy, Kevin
  • McGlory, Chris
  • Mitchell, Cameron J
  • Oikawa, Sara Y
  • Morton, Robert W
  • Phillips, Bethan E
  • Baker, Steven
  • Atherton, Phillip J
  • Wahlestedt, Claes
  • Phillips, Stuart

publication date

  • August 2020