title: Effect of chronic contractile activity on mRNA stability in skeletal muscle.
abstract: Repeated bouts of exercise promote the biogenesis of mitochondria by multiple steps in the gene expression patterning. The role of mRNA stability in controlling the expression of mitochondrial proteins is relatively unexplored. To induce mitochondrial biogenesis, we chronically stimulated (10 Hz; 3 or 6 h/day) rat muscle for 7 days. Chronic contractile activity (CCA) increased the protein expression of PGC-1alpha, c-myc, and mitochondrial transcription factor A (Tfam) by 1.6-, 1.7- and 2.0-fold, respectively. To determine mRNA stability, we incubated total RNA with cytosolic extracts using an in vitro cell-free system. We found that the intrinsic mRNA half-lives (t(1/2)) were variable within control muscle. Peroxisome proliferator-activated receptor-gamma, coactivator-1alpha (PGC-1alpha) and Tfam mRNAs decayed more rapidly (t(1/2) = 22.7 and 31.4 min) than c-myc mRNA (t(1/2) = 99.7 min). Furthermore, CCA resulted in a differential response in degradation kinetics. After CCA, PGC-1alpha and Tfam mRNA half-lives decreased by 48% and 44%, respectively, whereas c-myc mRNA half-life was unchanged. CCA induced an elevation of both the cytosolic RNA-stabilizing human antigen R (HuR) and destabilizing AUF1 (total) by 2.4- and 1.8-fold, respectively. Increases in the p37(AUF1), p40(AUF1), and p45(AUF1) isoforms were most evident. Thus these data indicate that CCA results in accelerated turnover rates of mRNAs encoding important mitochondrial biogenesis regulators in skeletal muscle. This adaptation is likely beneficial in permitting more rapid phenotypic plasticity in response to subsequent contractile activity.
authors.affiliation: School of Kinesiology and Health Science, York University, Toronto, ON, Canada.
authors.forename: Ruanne Y J
authors.initials: RY
authors.lastname: Lai
authors.forename: Vladimir
authors.initials: V
authors.lastname: Ljubicic
authors.forename: Donna
authors.initials: D
authors.lastname: D'souza
authors.forename: David A
authors.initials: DA
authors.lastname: Hood
mesh_terms: D020413:3' Untranslated Regions; D000222:Adaptation, Physiological; D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D001483:Base Sequence; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; D004558:Electric Stimulation; D006207:Half-Life; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008931:Mitochondria, Muscle / Q000378:metabolism*; D008969:Molecular Sequence Data; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000378:metabolism*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010641:Phenotype; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D020871:RNA Stability; D012333:RNA, Messenger / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D000954:Antigens, Surface; D051959:ELAV Proteins; D000067780:ELAV-Like Protein 1; C098770:ELAVL1 protein, human; C000630986:HNRNPD protein, human; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; C000630988:Hnrnpd protein, rat; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C489030:Tfam protein, rat; D014157:Transcription Factors