SLU7, also known as Splicing factor synergistic lethal with U5 snRNA 7, is a crucial splicing factor. It is necessary for the accurate selection of 3' splice sites, significantly influencing gene transcript diversity. Additionally, it serves as an integrative hub for different levels of gene expression regulation, including epigenetic DNA remodeling, transcription modulation, and protein stability [1].

In mouse models, SLU7 knockdown in human liver cells and mouse liver led to profound pre-mRNA splicing and gene expression changes, impairing glucose and lipid metabolism, hormonal responsiveness, and reverting to a fetal-like gene expression pattern. It also increased hepatocellular proliferation and induced a tumor-like glycolytic phenotype [3]. In ethanol-fed mice, hepatic knockdown of Slu7 ameliorated inflammation and liver injury, affecting the splicing of genes like SIRT1, lipin-1, and Srsf3 [4]. In animal models of liver injury, caspases activated during liver damage were responsible for the cleavage and degradation of SLU7, inhibiting nonsense-mediated RNA decay (NMD) [2].

In conclusion, SLU7 is central to maintaining liver homeostasis, regulating hepatocyte identity and quiescence. Its dysregulation is associated with liver diseases, such as alcoholic steatohepatitis and hepatocarcinogenesis. Studies using gene-knockout mouse models have revealed its role in key biological processes and disease conditions, providing insights into potential therapeutic targets for liver-related diseases.