Fig. 4.

Nonsense-mediated decay of aberrant transcripts and downregulation of target genes. a Relative expression of some target genes of mutant SF3B1-associated alternative 3′ splice sites in the SF3B1-mutated CD34+ cells as compared with those without SF mutations. Blue bars indicate expression levels of the authentic transcripts. Pink and red bars indicate those of the aberrant transcripts detected before and after CHX treatment, respectively. These genes had a seemingly small amount of the aberrant transcripts that increased after CHX treatment. b, c Volcano plots comparing PSI values of SF3B1-associated splicing alterations between samples with and without CHX treatment (n = 4 each). Alternative splicing events were separately plotted for non-truncating events (b) and truncating ones (c). X-axis indicates fold changes in PSI values after CHX treatment on a log₂ scale. Y-axis indicates P values on a negative log₁₀ scale. Transcripts increased after CHX treatment with a q-value <0.01 were regarded as sensitive to NMD. d A volcano plot comparing gene expression levels between the SF3B1-mutated CD34+ cells (n = 32) and those without known SF mutations (n = 41). X-axis indicates fold changes in gene expression on a log₂ scale. Y-axis indicates q-values on a negative log₁₀ scale. Target genes of mutant SF3B1-associated alternative 3′ splice sites and NMD are depicted in red