ArticleMolecular and cellular biology2014
Alteration of NCoR corepressor splicing in mice causes increased body weight and hepatosteatosis without glucose intolerance.
Article in Molecular and cellular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Therapeutic RNA-silencing oligonucleotides in metabolic diseases.Nature reviews. Drug discovery · 2022Review
- A cell type-specific expression map of NCoR1 and SMRT transcriptional co-repressors in the mouse brain.The Journal of comparative neurology · 2020Article
- Gene-Specific Actions of Transcriptional Coregulators Facilitate Physiological Plasticity: Evidence for a Physiological Coregulator Code.Trends in biochemical sciences · 2020Review
- Sleeve gastrectomy enhances glucose utilization and remodels adipose tissue independent of weight loss.American journal of physiology. Endocrinology and metabolism · 2020Article
- Specific ablation of the NCoR corepressor δ splice variant reveals alternative RNA splicing as a key regulator of hepatic metabolism.PloS one · 2020Article
- Evolution of NCoR-1 and NCoR-2 corepressor alternative mRNA splicing in placental mammals.BMC research notes · 2019Article
- Alternative mRNA Splicing in the Pathogenesis of Obesity.International journal of molecular sciences · 2018Review
- The actions of thyroid hormone signaling in the nucleus.Molecular and cellular endocrinology · 2017Review
- Corepressor diversification by alternative mRNA splicing is species specific.BMC evolutionary biology · 2016Article
- Mitotic Activation of a Novel Histone Deacetylase 3-Linker Histone H1.3 Protein Complex by Protein Kinase CK2.The Journal of biological chemistry · 2016Article
- Regulation of corepressor alternative mRNA splicing by hormonal and metabolic signaling.Molecular and cellular endocrinology · 2015Article
- Impacts of Alternative Splicing Events on the Differentiation of Adipocytes.International journal of molecular sciences · 2015Review
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Authors and funding
5 authors.
Funding
Abstract
Alternative mRNA splicing is an important means of diversifying function in higher eukaryotes. Notably, both NCoR and SMRT corepressors are subject to alternative mRNA splicing, yielding a series of distinct corepressor variants with highly divergent functions. Normal adipogenesis is associated with a switch in corepressor splicing from NCoRω to NCoRδ, which appears to help regulate this differentiation process. We report here that mimicking this development switch in mice by a splice-specific whole-animal ablation of NCoRω is very different from a whole-animal or tissue-specific total NCoR knockout and produces significantly enhanced weight gain on a high-fat diet. Surprisingly, NCoRω(-/-) mice are protected against diet-induced glucose intolerance despite enhanced adiposity and the presence of multiple additional, prodiabetic phenotypic changes. Our results indicate that the change in NCoR splicing during normal development both helps drive normal adipocyte differentiation and plays a key role in determining a metabolically appropriate storage of excess calories. We also conclude that whole-gene "knockouts" fail to reveal how important gene products are customized, tailored, and adapted through alternative mRNA splicing and thus do not reveal all the functions of the protein products of that gene.
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Registered trials
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