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Exercise training increases the expression and nuclear localization of mRNA destabilizing proteins in skeletal muscle

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AJP Regulatory Integrative and Comparative Physiology

Published online on

Abstract

While a paucity of information exists regarding post-transcriptional mechanisms influencing mitochondrial biogenesis, in resting muscle the stability of peroxisome proliferator-activated receptor co-activator 1α (PGC-1α) mRNA has been linked to mitochondrial content. Therefore, in the current study we have examined if exercise promotes mRNA accumulation through the induction of proteins affiliated with mRNA stabilization (HuR) or conversely by decreasing the expression of mRNA destabilizing proteins (AUF1 and CUG-BP1). A single bout of exercise increased (P<0.05) the mRNA content of the transcriptional co-activator PGC-1α ~3.5 fold without affecting mRNA content for HuR, CUG-BP1 or AUF1. One week of treadmill exercise training did not alter markers of mitochondrial content, the mRNA stabilizing protein HuR, or the mRNA destabilizing protein AUF1. In contrast, the mRNA destabilizing protein CUG-BP1 increased ~40%. Four weeks of treadmill training increased the content of subunits of the electron transport chain ~50%, suggesting induction of mitochondrial biogenesis. Expression levels for HuR and CUG-BP1 were not altered with chronic training; however AUF1 expression was increased post-training. Specifically, training increased (P<0.05) total muscle expression of two of the four AUF1 isoforms ~50% (AUF1p37, AUF1p40). Interestingly, these two isoforms were not detected in isolated nuclei; however, a large band representing the other two isoforms (AUF1p42, AUF1p45) was present in nuclei and increased ~35% following chronic training. Altogether the current data provides evidence that mitochondrial biogenesis occurs in the presence of increased CUG-BP1 and AUF1 following, suggesting that reductions in known mRNA destabilizing proteins likely does not contribute to exercise-induced mitochondrial biogenesis.