Fig. 10: Proposed mechanism of cell death in SRSF1-deficient hepatocytes.
From: Splicing factor SRSF1 deficiency in the liver triggers NASH-like pathology and cell death
Loss of SRSF1 initially leads to an overwhelming accumulation of R-loops within the actively transcribed DNA of hepatocytes. This results in widespread DNA damage as unresolved R-loops are prone to double-stranded breaks. The combined effects of SRSF1 activity loss, R-loop accumulation, and DNA damage response causes a halt in global transcription. With decreased mRNA synthesis and export, there is diminished translation and protein production which leads to subsequent cell death and hepatic failure.
