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

Here we show that, when compared to control mice, muscle specific HuR knockout (muHuR-KO) animals have higher exercise endurance that is associated with a significant increase in oxygen consumption and carbon dioxide production. Histological analysis demonstrates that the absence of HuR significantly enhances the proportion of oxidative type I fibers in several skeletal muscles, showing that under normal conditions, HuR promotes the formation of glycolytic type II fibers. HuR mediates this outcome by collaborating with the mRNA decay factor KSRP, to destabilize the PGC-1α mRNA, a well-known promoter of type I fiber formation. Furthermore, the type I fiber-enriched phenotype of muHuR-KO mice is associated with a protection against cancer cachexia-induced muscle wasting mRNA profiles of Control and muscle specif HuR ko mice was generated by RNA-seq from sckeletal muscle samples in duplicate using Illumina NextSeq 500 platform.