METTL3 inhibits inflammation of retinal pigment epithelium cells by regulating NR2F1 in an m6A-dependent manner [meRIP-seq]

To investigate the fuction of METTL3 in autoimmune uveitis, we established ARPE-19 cell lines in which target gene has been knocked down by shRNA. Overall design: In this study, we explored the effects and underlying mechanisms of methyltransferase-like 3 (METTL3) in retinal pigment epithelium (RPE) cells, which are crucial for the pathogenesis of autoimmune uveitis. Our results showed that the expression of METTL3 was increased in both human RPE (hRPE) cells and ARPE19 cells after lipopolysaccharide (LPS) stimulation. Moreover, these two types of RPE cells exhibited inhibited proliferation and increased barrier destruction and inflammatory factor secretion after METTL3 silencing. Mechanistically, we found that NR2F1, as a METTL3-methylated target gene, promotes the inflammation of RPE cells in an m6A-dependent manner. Interestingly, NR2F1 deficiency reversed the increased inflammation in the METTL3-defective RPE cells. In conclusion, our study revealed that METTL3 attenuates RPE cell inflammation by methylating NR2F1, suggesting the critical role of METTL3 in RPE cells.