RUNX1 deficiency dramatically affects global RNA spicing. (A) Volcano plots of significantly altered splice events in SRSF2^P95H/+/+, RUNX1 knockdown, and double mutant K562 cells compared with WT cells. (B) Venn diagram showing the overlap between splicing events that were significantly dysregulated in single/double mutant K562 cells relative to WT cells. (C) Volcano plots of significantly altered splice events in Srsf2^P95H/+, Runx1 knockout, and double mutant murine LK cells compared with WT LK cells. (D) Venn diagram showing the overlap between splicing events that were significantly dysregulated in single/double mutant LK cells relative to WT LK cells. (E) Scatter plots showing the use of 4, 5, or 6-mer nucleotide sequences on promoted vs repressed exons in single/double mutant cells relative to WT K562 cells. (F) Bar plots quantifying the enrichment of CCNG/GGNG (N = any nucleotide) exonic splicing enhancer motifs adjacent to differentially spliced cassette exons that were promoted vs repressed in single/double mutant K562 cells relative to WT K562 cells (SRSF2^P95H/+/+: P < 2.2e-16; RUNX1 knockdown: P = 1.18e-6; double mutant: P < 2.2e-16). (G) Scatter plots showing the use of 4, 5, or 6-mer nucleotide sequences on promoted vs repressed exons in single/double mutant murine LK cells relative to WT LK cells. (H) Bar plots quantifying the enrichment of CCNG/GGNG exonic splicing enhancer motifs adjacent to differentially spliced cassette exons that were promoted vs repressed in single/double mutant murine LK cells relative to WT cells (Srsf2^P95H/+: P < 2.2e-16; Runx1 knockout: P = .1443; Double mutant: P < 2.2e-16). FDR, false discovery rate.