Fig. 6.

Sequestration of MBNL1 to RNA foci within corneal explant tissue. A. MBNL1 is sequestered to the RNA foci within the corneal endothelium of only CTG18.1 expansion-positive FECD patient-derived tissues, scale bar 5 μM. B. Schematic illustrating that in the absence of CTG18.1 expansions, MBNL1 is soluble within the nucleus. C. In the presence of a CTG18.1 expansion, levels of functional MBNL1 are depleted due to the sequestration of the splicing factor to hairpin structures formed by the RNAs comprising expanded copies of TCF4 transcripts. D. Schematic depicting hypothesised mechanism of splicing dysregulation observed within expansion-positive corneal endothelial cells where the sequestering of splicing factors to hairpin structures formed by TCF4 RNA transcripts results in widespread dysregulation of pre-mRNA splicing. Permission for re-use of (A) from Du et al. (2015) was granted through CC-BY license (https://creativecommons.org/licenses/by/4.0/legalcode).