title: Exercise training increases the expression and nuclear localization of mRNA destabilizing proteins in skeletal muscle.
abstract: While a paucity of information exists regarding posttranscriptional mechanisms influencing mitochondrial biogenesis, in resting muscle the stability of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) mRNA has been linked to mitochondrial content. Therefore, in the current study we have examined whether exercise promotes mRNA accumulation through the induction of proteins affiliated with mRNA stabilization (human antigen R, HuR) or conversely by decreasing the expression of mRNA destabilizing proteins [AU-rich binding factor (AUF1) and CUG binding protein (CUG-BP1)]. A single bout of exercise increased (P < 0.05) the mRNA content of the transcriptional coactivator 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 posttraining. Specifically, training increased (P < 0.05) total muscle expression of two of four AUF1 isoforms ∼50% (AUF1(p37), AUF1(p40)). Interestingly, these two isoforms were not detected in isolated nuclei; however, a large band representing the other two isoforms (AUF1(p42), AUF1(p45)) 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, suggesting that reductions in known mRNA destabilizing proteins likely does not contribute to exercise-induced mitochondrial biogenesis.
authors.affiliation: Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, Ontario, Canada.
authors.forename: Sarthak
authors.initials: S
authors.lastname: Matravadia
authors.forename: Vanessa B
authors.initials: VB
authors.lastname: Martino
authors.forename: Daniel
authors.initials: D
authors.lastname: Sinclair
authors.forename: David M
authors.initials: DM
authors.lastname: Mutch
authors.forename: Graham P
authors.initials: GP
authors.lastname: Holloway
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D000067879:CELF1 Protein; D051959:ELAV Proteins / Q000235:genetics / Q000378:metabolism; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008931:Mitochondria, Muscle / Q000378:metabolism; D063269:Mitochondrial Turnover; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D005082:Physical Exertion; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D012420:Running; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000067879:CELF1 Protein; C502743:CELF1 protein, mouse; D051959:ELAV Proteins; C000630986:HNRNPD protein, human; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; C000630987:Hnrpd protein, mouse; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014157:Transcription Factors
keywords: AUF1; PGC-1α; mRNA stability; mitochondrial biogenesis