ArticleMolecular and cellular biology2016
Liver-Specific Deletion of SRSF2 Caused Acute Liver Failure and Early Death in Mice.
Article in Molecular and cellular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Decoding the role of aberrant RNA alternative splicing in hepatocellular carcinoma: a comprehensive review.Journal of cancer research and clinical oncology · 2023Pooled it
- Epigallocatechin Gallate Influences in Acute Respiratory Distress Syndrome by Regulating Gut Microbiota: Current Research Status and Therapeutic Prospects.Journal of inflammation research · 2026Review
- Biological functions of 5-methylcytosine RNA-binding proteins and their potential mechanisms in human cancers.Frontiers in oncology · 2025Review
- Implications for metabolic disturbances in myelodysplastic syndromes.Seminars in hematology · 2024Review
- Article
- Review
- Dysregulation of RNA splicing in early non-alcoholic fatty liver disease through hepatocellular carcinoma.Scientific reports · 2024Article
- Splicing factor SRSF1 deficiency in the liver triggers NASH-like pathology and cell death.Nature communications · 2023Article
- Increased Expression of SRSF1 Predicts Poor Prognosis in Multiple Myeloma.Journal of oncology · 2023Article
- Single-Cell RNA Sequencing Reveals Heterogeneity of Myf5-Derived Cells and Altered Myogenic Fate in the Absence of SRSF2.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- SRSF1 governs progenitor-specific alternative splicing to maintain adult epithelial tissue homeostasis and renewal.Developmental cell · 2022Article
- Neuronal Pnn Deficiency Increases Oxidative Stress and Exacerbates Cerebral Ischemia/Reperfusion Injury in Mice.Antioxidants (Basel, Switzerland) · 2022Article
- Rare coding variants in 35 genes associate with circulating lipid levels-A multi-ancestry analysis of 170,000 exomes.American journal of human genetics · 2022Article
- Splicing factor Srsf5 deletion disrupts alternative splicing and causes noncompaction of ventricular myocardium.iScience · 2021Article
- Alternative RNA Splicing in Fatty Liver Disease.Frontiers in endocrinology · 2021Review
- Splicing Factor SRSF1 Is Essential for Satellite Cell Proliferation and Postnatal Maturation of Neuromuscular Junctions in Mice.Stem cell reports · 2020Article
- Effect of PFOA on DNA Methylation and Alternative Splicing in Mouse Liver.Toxicology letters · 2020Article
- Loss of SRSF2 triggers hepatic progenitor cell activation and tumor development in mice.Communications biology · 2020Article
- Alternative Splicing in Hepatocellular Carcinoma.Cellular and molecular gastroenterology and hepatology · 2020Review
- Modeling RNA-Binding Protein Specificity In Vivo by Precisely Registering Protein-RNA Crosslink Sites.Molecular cell · 2019Article
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The liver performs a variety of unique functions critical for metabolic homeostasis. Here, we show that mice lacking the splicing factor SRSF2 but not SRSF1 in hepatocytes have severe liver pathology and biochemical abnormalities. Histological analyses revealed generalized hepatitis with the presence of ballooned hepatocytes and evidence of fibrosis. Molecular analysis demonstrated that SRSF2 governs splicing of multiple genes involved in the stress-induced cell death pathway in the liver. More importantly, SRSF2 also functions as a potent transcription activator, required for efficient expression of transcription factors mainly responsible for energy homeostasis and bile acid metabolism in the liver. Consistent with the effects of SRSF2 in gene regulation, accumulation of total cholesterol and bile acids was prominently observed in the mutant liver, followed by enhanced generation of reactive oxygen species and increased endoplasmic reticulum stress, as revealed by biochemical and ultrastructural analyses. Taking these observations together, inactivation of SRSF2 in liver caused dysregulated splicing events and hepatic metabolic disorders, which trigger endoplasmic reticulum stress, oxidative stress, and finally liver failure.
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