ArticleThe Journal of biological chemistry2016
Peroxisome Proliferator-activated Receptor γ Coactivator-1 α Isoforms Selectively Regulate Multiple Splicing Events on Target Genes.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Effectiveness and safety of blood flow restriction training for patients with type 2 diabetes mellitus: a systematic review with meta analysis.BMC sports science, medicine & rehabilitation · 2026Pooled it
- High-intensity leg cycling alters the molecular response to resistance exercise in the arm muscles.Scientific reports · 2021Trial
- Molecular regulation of PGC-1α: from protein-protein interactions and post-translational modifications to pharmacological modulation.Journal of molecular medicine (Berlin, Germany) · 2026Review
- Article
- Deciphering the PGC-1α-TFAM Axis in Parkinson's Disease (PD) - A Mechanism Approach Targeting Therapeutics for PD.Molecular neurobiology · 2025Review
- Neuron-specific isoform of PGC-1α regulates neuronal metabolism and brain aging.Nature communications · 2025Article
- Mechanistic Insights into Alternative Gene Splicing in Oxidative Stress and Tissue Injury.Antioxidants & redox signaling · 2024Review
- CARM1 drives mitophagy and autophagy flux during fasting-induced skeletal muscle atrophy.Autophagy · 2024Article
- Peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family in physiological and pathophysiological process and diseases.Signal transduction and targeted therapy · 2024Review
- Commercially available PGC-1α antibodies vary greatly in specificity and sensitivity.microPublication biology · 2024Article
- AAV-Mediated nuclear localized PGC1α4 delivery in muscle ameliorates sarcopenia and aging-associated metabolic dysfunctions.Aging cell · 2023Article
- Ginsenosides Rc, as a novel SIRT6 activator, protects mice against high fat diet induced NAFLD.Journal of ginseng research · 2023Article
- PGC-1α senses the CBC of pre-mRNA to dictate the fate of promoter-proximally paused RNAPII.Molecular cell · 2023Article
- Association of rare PPARGC1A variants with Parkinson's disease risk.Journal of human genetics · 2022Article
- Article
- Aerobic exercise elicits clinical adaptations in myotonic dystrophy type 1 patients independently of pathophysiological changes.The Journal of clinical investigation · 2022Article
- Epigenetics of Mitochondria-Associated Genes in Striated Muscle.Epigenomes · 2021Article
- Oxidative Stress and Hypoxia Modify Mitochondrial Homeostasis During Glaucoma.Antioxidants & redox signaling · 2021Article
- Mitochondrial Quality Control in Sarcopenia: Updated Overview of Mechanisms and Interventions.Aging and disease · 2021Review
- RNA-bound PGC-1α controls gene expression in liquid-like nuclear condensates.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
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Authors and funding
14 authors.
Funding
Abstract
Endurance and resistance exercise training induces specific and profound changes in the skeletal muscle transcriptome. Peroxisome proliferator-activated receptor γ coactivator-1 α (PGC-1α) coactivators are not only among the genes differentially induced by distinct training methods, but they also participate in the ensuing signaling cascades that allow skeletal muscle to adapt to each type of exercise. Although endurance training preferentially induces PGC-1α1 expression, resistance exercise activates the expression of PGC-1α2, -α3, and -α4. These three alternative PGC-1α isoforms lack the arginine/serine-rich (RS) and RNA recognition motifs characteristic of PGC-1α1. Discrete functions for PGC-1α1 and -α4 have been described, but the biological role of PGC-1α2 and -α3 remains elusive. Here we show that different PGC-1α variants can affect target gene splicing through diverse mechanisms, including alternative promoter usage. By analyzing the exon structure of the target transcripts for each PGC-1α isoform, we were able to identify a large number of previously unknown PGC-1α2 and -α3 target genes and pathways in skeletal muscle. In particular, PGC-1α2 seems to mediate a decrease in the levels of cholesterol synthesis genes. Our results suggest that the conservation of the N-terminal activation and repression domains (and not the RS/RNA recognition motif) is what determines the gene programs and splicing options modulated by each PGC-1α isoform. By using skeletal muscle-specific transgenic mice for PGC-1α1 and -α4, we could validate, in vivo, splicing events observed in in vitro studies. These results show that alternative PGC-1α variants can affect target gene expression both quantitatively and qualitatively and identify novel biological pathways under the control of this system of coactivators.
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