The impact of the Sprtn mutation on gene expression in liver tissue

Biallelic mutations in the SPRTN gene cause an autosomal recessive progeroid disease known as Ruijs–Aalfs syndrome. Patients with Ruijs–Aalfs syndrome display symptoms of premature ageing and typically develop hepatocellular carcinoma during adolescence. To study the functional role of this protein, we generated knock-in mice (Sprtn Y118C/Y118C) that largely recapitulate the Ruijs–Aalfs phenotype. These mice harbour the equivalent of the Y117C missense mutation described in Ruijs–Aalfs patients. SPRTN has recently been implicated in DNA repair, specifically in the resolution of DNA–protein crosslinks (DPCs), which facilitates replisome bypass and allows translesion synthesis across DPC adducts. Understanding this DNA repair pathway is of paramount importance, as cells lacking SPRTN are not viable, and DNA–protein lesions can be induced by UV light, ionizing radiation, or normal cellular metabolism. Moreover, a broad spectrum of chemotherapeutic drugs induces protein–DNA crosslinking. In our study, we compared the bulk transcriptome of Sprtn Y118C/Y118C and wild-type mice using RNA extracted from liver tissue.