Loss of METTL3 induces IFN signaling upon PRMT5 inhibition. (A) Enriched pathways within upregulated genes in KO cells (analyzed using “Enrichr”; https://maayanlab.cloud/Enrichr/). (B) Volcano plot depicting up and downregulated genes upon METTL3 KO. (C) Heatmap showing the expression pattern of IFN pathway signaling genes. Z-scores were calculated for each gene using DESeq2 normalized counts. Gene expression clustering was performed using the Euclidean distance and complete linkage method. mRNA expression of (D) IFIT genes and (E) IRFs in WT, METTL3 KO - DMSO and GSK595-treated cells (normalized to WT DMSO). (F) Validation of METTL3 overexpression in CAL-1 cells. (G) Expression of IFIT1 in WT and METTL3 OE cells after GSK595 treatment. Data are shown as mean ± standard error of the mean of 3 independent experiments. *P < .05; **P < .01; P < .001.