PRMT5 inhibition causes increased IR in genes associated with RNA methylation. (A) Increase in IR events in the treated group compared to the DMSO control group. (B) Biological processes are overrepresented among genes with increased IR. (C) GSEA plots illustrating gene sets affected by GSK595 treatment. (D) Decrease in expression of genes associated with RNA methylation after treatment with GSK595 (0.31 and 5 µM). (E) A dose-dependent increase in IR transcripts of METTL3 after PRMT5 inhibition. Decrease in (F) mRNA expression of PRMT5 and METTL3 (normalized to DMSO) and (G) protein levels of PRMT5, METTL3, MYC, and cleaved caspase-3 after GSK595 treatment. (H) Dose-dependent reduction in m6A activity in treated cells normalized to DMSO. Data are shown as mean ± standard error of the mean of 3 independent experiments. *P < .05; **P < .01. GSEA, gene set enrichment.