ArticleThe Journal of clinical investigation2019
Degradation of splicing factor SRSF3 contributes to progressive liver disease.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 1 of them a synthesis that pooled it.
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Who cites it
67 citing papers in PubMed, 1 synthesis or guideline pooled it, 115 citations in OpenAlex.
- Decoding the role of aberrant RNA alternative splicing in hepatocellular carcinoma: a comprehensive review.Journal of cancer research and clinical oncology · 2023Pooled it
- SRSF3 plays a key role in liver cancer sex disparity by facilitating hepatocyte expression of ERα and FOXA.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Protein neddylation as a therapeutic target: challenges and opportunities.The Journal of clinical investigation · 2026Review
- Splicing of ultraconserved poison exons controls mitotic fidelity and stem cell viability.bioRxiv : the preprint server for biology · 2026Article
- Decoding neddylation in malignancies: molecular mechanisms, biological functions, therapeutic resistance, and clinical potential.Cell death & disease · 2026Review
- SRSF3-TRIM28-MDC1 prevents DNA damage caused by R-loops in fatty liver disease in mice.JCI insight · 2026Article
- Integrated analysis of RNA-binding proteins in MAFLD: mechanistic insights and diagnostic biomarker potential via alternative splicing.Journal of bioenergetics and biomembranes · 2025Article
- Early alternative splicing signatures and RBP networks in MASLD progression to cirrhosis.BMC medical genomics · 2025Article
- Dysregulated RNA splicing impairs regeneration in alcohol-associated liver disease.Nature communications · 2025Article
- Alternative Splicing Regulation in Metabolic Disorders.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025Review
- Deciphering the roles of neddylation modification in hepatocellular carcinoma: Molecular mechanisms and targeted therapeutics.Genes & diseases · 2025Review
- The ubiquitin-proteasome system: A potential target for the MASLD.Acta pharmaceutica Sinica. B · 2025Review
- Alternative splicing: hallmark and therapeutic opportunity in metabolic liver disease.Gastroenterology report · 2025Review
- Regulation of Alternative Splicing of Lipid Metabolism Genes in Sepsis-Induced Liver Damage by RNA-Binding Proteins.Inflammation · 2024Article
- Disrupted Post-Transcriptional Regulation of Gene Expression as a Hallmark of Fatty Liver Progression.International journal of molecular sciences · 2024Article
- Review
- Expression of Truncated Products at the 5'-Terminal Region of RIPK2 and Evolutive Aspects that Support Their Biological Importance.Genome biology and evolution · 2024Article
- Factors affecting the expression and stability of full-length and truncated SRSF3 proteins in human cancer cells.Scientific reports · 2024Article
- SRSF3 Knockdown Inhibits Lipopolysaccharide-Induced Inflammatory Response in Macrophages.Current issues in molecular biology · 2024Article
- The Many Roads from Alternative Splicing to Cancer: Molecular Mechanisms Involving Driver Genes.Cancers · 2024Review
7 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Serine rich splicing factor 3 (SRSF3) plays a critical role in liver function and its loss promotes chronic liver damage and regeneration. As a consequence, genetic deletion of SRSF3 in hepatocytes caused progressive liver disease and ultimately led to hepatocellular carcinoma. Here we show that SRSF3 is decreased in human liver samples with non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), or cirrhosis that was associated with alterations in RNA splicing of known SRSF3 target genes. Hepatic SRSF3 expression was similarly decreased and RNA splicing dysregulated in mouse models of NAFLD and NASH. We showed that palmitic acid-induced oxidative stress caused conjugation of the ubiquitin like NEDD8 protein to SRSF3 and proteasome mediated degradation. SRSF3 was selectively neddylated at lysine11 and mutation of this residue (SRSF3-K11R) was sufficient to prevent both SRSF3 degradation and alterations in RNA splicing. Finally prevention of SRSF3 degradation in vivo partially protected mice from hepatic steatosis, fibrosis and inflammation. These results highlight a neddylation-dependent mechanism regulating gene expression in the liver that is disrupted in early metabolic liver disease and may contribute to the progression to NASH, cirrhosis and ultimately hepatocellular carcinoma.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.