Figure 4
Mouse and human SF3B1-K700E share aberrant splicing properties, but affect different mRNA transcripts. (a) Comparison of consensus sequences upstream of aberrant and canonical 3′ ss shows a striking preservation of these motifs between mouse Sf3b1K700E/+ lin− cells and several human SF3B1-mutant cancers. (b) Distribution of distances of aberrant 3′ss (AG) from the downstream canonical AG is also strikingly similar between mouse Sf3b1K700E/+ lin− cells and human cancer samples. (c) By contrast, a comparison of genes found to be aberrantly spliced in human vs mouse samples shows minimal overlap. (d) Poor sequence preservation in the mouse of the aberrant splice sites affecting human genes TMEM14C and ABCB7 that are thought to trigger the formation of ring sideroblasts in MDS. (e) Volcano plots comparing mRNA expression between Sf3b1K700E/+ vs Sf3b1+/+ BM and lin− cells. The mRNA expression of genes Slc25a37, Tmem14c, Alas2 and Abcb7, thought to be involved in the formation of ring sideroblasts, is not significantly altered by the K700E mutation in mice. The number of aberrant events used to generate images in a and b is indicated in b (brackets). BRCA, breast cancer; CLL, chronic lymphocytic leukemia; MDS, myelodysplastic syndromes; SKCM, skin cutaneous melanoma.
