ArticleNature communications2023
Splicing factor SRSF1 deficiency in the liver triggers NASH-like pathology and cell death.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
33 citing papers in PubMed, 2 syntheses or guidelines pooled it, 43 citations in OpenAlex.
- The role of R-loops-mediated epigenetic regulation in genome stability maintenance and disease pathogenesis: a systematic review.Epigenetics · 2026Pooled it
- Decoding the role of aberrant RNA alternative splicing in hepatocellular carcinoma: a comprehensive review.Journal of cancer research and clinical oncology · 2023Pooled it
- PRMT5-mediated intron retention triggers innate and adaptive immunity against cancer.EMBO molecular medicine · 2026Article
- Landscape of splicing factors in early-onset gastric cancer reveals SRSF1 as a key driver of oxaliplatin resistance.The Journal of biological chemistry · 2026Article
- SRSF3-TRIM28-MDC1 prevents DNA damage caused by R-loops in fatty liver disease in mice.JCI insight · 2026Article
- MetaboMiNR: An Online Tool to Analyze Label-Free Proteomic Experiments With a Focus on Metabolism and Nuclear Receptors.Endocrinology · 2026Article
- Reduced R-loop abundance at proinflammatory loci: a shared epigenetic mechanism in inflammatory and metabolic diseases.Frontiers in cardiovascular medicine · 2026Article
- 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
- Article
- R-loops: a key driver of inflammatory responses in cancer.Experimental & molecular medicine · 2025Review
- SRSF1-mediated alternative splicing regulates bladder cancer progression and cisplatin sensitivity through HIF1A/BNIP3/mitophagy axis.Journal of translational medicine · 2025Article
- R-loops as a trigger for intra- and extrachromosomal DNA amplification in cancer.Frontiers in cell and developmental biology · 2025Review
- Looping forward: exploring R-loop processing and therapeutic potential.FEBS letters · 2025Review
- Mechanisms underlining R-loop biology and implications for human disease.Frontiers in cell and developmental biology · 2025Review
- Alternative splicing: hallmark and therapeutic opportunity in metabolic liver disease.Gastroenterology report · 2025Review
- Split-APEX implicates splicing factor SRSF1 and splicing helicases in ribosomal biogenesis.Frontiers in molecular biosciences · 2025Article
- AAV-mediated genome editing is influenced by the formation of R-loops.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Splicing factor SRSF1 attenuates cardiomyocytes apoptosis via regulating alternative splicing of Bcl2L12.Cell & bioscience · 2024Article
- Mechanistic role of long non-coding RNAs in the pathogenesis of metabolic dysfunction-associated steatotic liver disease and fibrosis.eGastroenterology · 2024Article
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 2 countries.
Funding
Abstract
Regulation of RNA processing contributes profoundly to tissue development and physiology. Here, we report that serine-arginine-rich splicing factor 1 (SRSF1) is essential for hepatocyte function and survival. Although SRSF1 is mainly known for its many roles in mRNA metabolism, it is also crucial for maintaining genome stability. We show that acute liver damage in the setting of targeted SRSF1 deletion in mice is associated with the excessive formation of deleterious RNA-DNA hybrids (R-loops), which induce DNA damage. Combining hepatocyte-specific transcriptome, proteome, and RNA binding analyses, we demonstrate that widespread genotoxic stress following SRSF1 depletion results in global inhibition of mRNA transcription and protein synthesis, leading to impaired metabolism and trafficking of lipids. Lipid accumulation in SRSF1-deficient hepatocytes is followed by necroptotic cell death, inflammation, and fibrosis, resulting in NASH-like liver pathology. Importantly, SRSF1-depleted human liver cancer cells recapitulate this pathogenesis, illustrating a conserved and fundamental role for SRSF1 in preserving genome integrity and tissue homeostasis. Thus, our study uncovers how the accumulation of detrimental R-loops impedes hepatocellular gene expression, triggering metabolic derangements and liver damage.
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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.