RGD Reference Report - Effect of chronic contractile activity on mRNA stability in skeletal muscle. - Rat Genome Database

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Effect of chronic contractile activity on mRNA stability in skeletal muscle.

Authors: Lai, RY  Ljubicic, V  D'souza, D  Hood, DA 
Citation: Lai RY, etal., Am J Physiol Cell Physiol. 2010 Jul;299(1):C155-63. doi: 10.1152/ajpcell.00523.2009. Epub 2010 Apr 7.
RGD ID: 10040990
Pubmed: PMID:20375275   (View Abstract at PubMed)
PMCID: PMC2904257   (View Article at PubMed Central)
DOI: DOI:10.1152/ajpcell.00523.2009   (Journal Full-text)

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.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
HnrnpdRatresponse to electrical stimulus  IEP  RGD 
Ppargc1aRatresponse to electrical stimulus  IEP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hnrnpd  (heterogeneous nuclear ribonucleoprotein D)
Ppargc1a  (PPARG coactivator 1 alpha)


Additional Information