FIGURE 1

FIGURE 1

SORBS1 exon 25 is misregulated in skeletal muscle biopsies from DM1 patients. (a) List of 30 enriched DSEs identified in common in DM1, DKO MBNL1/2 and WT hiPSC‐derived skeletal muscle cells in bulk transcriptomic analysis. For alternative splicing analysis, exons have been numbered according to FasterDB database. (b) RT‐qPCR analysis of SORBS1 exon 25 inclusion and total SORBS1 mRNA in hiPSC‐derived skeletal muscle cells from WT, DM1 and DKO MBNL1/2. (N = 4 independent experiments, ****p < 0.0001; ***p < 0.001; *p < 0.01, one‐way ANOVA followed by Tukey's post hoc test). (c) RT‐PCR analysis of SORBS1 exon 25 alternative splicing in human skeletal muscle samples from control (CTL) and congenital DM1 fetuses (DM1). (d) Violin plots of SORBS1 exon 25, BIN1 exon 11 and DMD exon 78 inclusion in tibialis anterior muscles samples from control and DM1 patients obtained from the publicly available DMseq database. Ctrl (N = 11); DM1 (N = 40). (****p < 0.00001; ***p < 0.0001, one‐way ANOVA followed by Tukey's post hoc test). (e) AlphaFold analysis of the SORBS1 tridimensional structure. The sequences highlighted in red correspond to the exon 25. (f) Schematic diagram of the SoHo domain and the three SH3 domains of the SORBS1 protein. Black squares represent coding exons, and the red box corresponds to the exon 25.