IR induces YTHDF2 to degrade m6A-bound mRNA in the Notch signaling pathway. (A) Schematic illustration on the analysis strategy for identifying YTHDF2-bound and m⁶A-modified gene transcripts. (B) Venn diagram of overlapping genes from mRNA-seq that were downregulated following WT+IR versus WT and upregulated following Ythdf2-cKO+IR versus WT+IR. (C) Twin-volcano plot of genes with differential expression levels in the DCs (left: cKO+IR versus WT+IR; right: WT+IR versus WT), m⁶A marked genes (m⁶A-seq) are shown with green circles, YTHDF2 marked genes (RIP-seq) are shown with purple circles, and both m6A and YTHDF2 marked genes are shown with red circles. 86 target genes of YTHDF2 shown in upregulated cKO+IR versus WT+IR region and downregulated WT+IR versus WT region are represented with black circles. (D) GO enrichment pathway analysis using 86 YTHDF2 target genes in the context of IR. (E) Sankey flow diagrams of specific genes categorized in each enriched pathway in D. (F) Induction of NICD from BMDCs with single or triple KD of Mfng, Aph-1b, and Aph-1c (n = 3). Statistical analysis was performed using two-sided unpaired Student’s t test (F); **P < 0.01. Data are represented as the mean ± SEM.