SLU7, also known as Splicing factor synergistic lethal with U5 snRNA 7, is a crucial factor in gene expression regulation. Initially identified as a splicing factor essential for accurate 3' splice site selection, it significantly impacts gene transcript diversity. Additionally, it serves as an integrative hub for various levels of gene expression regulation, including epigenetic DNA remodeling, transcription modulation, and protein stability control. It is involved in multiple biological processes such as liver differentiation, genome integrity maintenance, and proper cell cycle progression [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, making cells refractory to key metabolic hormones, and reverting to a fetal-like gene expression pattern. Loss of SLU7 also increased hepatocellular proliferation and induced a tumor-like glycolytic phenotype [2]. In ethanol-fed mice, hepatic knockdown of Slu7 ameliorated inflammation and attenuated liver injury by regulating the splicing of genes like SIRT1, lipin-1, and Srsf3 [3].

In conclusion, SLU7 is a central regulator of hepatocyte identity and quiescence, playing a vital role in maintaining liver homeostasis. Its dysregulation is associated with liver diseases, including alcoholic steatohepatitis. Studies using gene knockdown in mouse models have revealed its significance in specific biological processes and disease conditions, providing insights into potential therapeutic strategies for liver-related diseases.