Dose-Dependent Regulation of Alternative Splicing by MBNL Proteins Reveals Biomarkers for Myotonic Dystrophy
Fig 6
(A) In our HEK293 inducible model, free [MBNL1] can be titrated by administration of doxycycline (top panel). In myotonic dystrophy, free [MBNL] proteins are titrated by sequestration to toxic CUG RNA (bottom panel). (B) Deletion of YGCY sites within the ultraconserved intron upstream of MBNL1 exon 5 influences dose-dependent curve parameters EC50, slope, both, or neither. (C) Biomarkers are most informative in the regions with a non-zero slope (red parts of curve). The best biomarkers also tend to have a broad dynamic range (Ψmax- Ψmin).