Fig. 8
Model of splicing alteration in myotonic dystrophy. a, b Lifespan in days of control and expanded CCUG (a) or CUG (b) expressing flies with or without expression of GFP-tagged rbFOX1. Flies expressing expanded CCUG or CUG repeats showed a median life of 10 and 21 days, respectively, which was significantly reduced in comparison to control flies (n = 50 flies, p < 0.0001, Gehan-Breslow-Wilcoxon test). Expression of rbFOX1 partly corrects median life and lifespan in CCUG expressing flies (n = 50 flies, CCUG rbFOX1 L1 p < 0.0001 and CCUG rbFOX1 L2 p = 0.0002). In contrast, expression of rbFOX1 does not improve lifespan of CUG expressing flies. c In myotonic dystrophy type 1, expanded CUG repeats represent an excess of ligand for MBNL proteins, resulting in their titration and sequestration in discrete nuclear RNA foci, ultimately resulting in alternative splicing changes that are inadequate to adult physiology. d In myotonic dystrophy type 2, expanded CCUG repeats also titrate MBNL proteins, but with a lesser efficiency due to competition with rbFOX proteins, which ultimately results in milder alternative splicing changes and milder symptoms compared to DM1
