NSUN2-mediated 5-methylcytosine enhances purine metabolism through ALYREF in retinoblastoma

5-methylcytosine (m5C) RNA modification installed by methyltransferase NSUN2 regulates gene expression and cell fate. Retinoblastoma (RB) is the most common primary intraocular tumor in children. However, the functional role of m5C modification in retinoblastoma remains unclear. Here, we show that 5-methylcytosine significantly promotes the progression of retinoblastoma. Retinoblastoma samples showed increased m5C levels, indicating a poor prognosis. Changes in global m5C modification were highly associated with tumor progression in vitro and in vivo. Mechanistically, NSUN2 stabilized the methylated PFAS mRNA, a tumor promoter in retinoblastoma. Our work uncovers a critical function for m5C methylation in retinoblastoma and provides additional insight into the understanding of m5C modification. Overall design: RNA-seq and MeRIP-seq for retinoblastoma cell lines (Y79) and one retina pigment epithelium cell line (ARPE-19)