PloS one · 2025
Transcriptomic analysis implicates the involvement of RBM20 in Fuchs' endothelial corneal dystrophy with TCF4 repeat expansion.
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Zhang Xunzhi, Yu Ze, Westfall Aundrea K, Han Kunyi, Mootha V Vinod, Xing Chao
Аннотация
BACKGROUND: Late-onset Fuchs' endothelial corneal dystrophy (FECD) is a degenerative disease of cornea manifesting during the fourth decade of life or later. An intronic trinucleotide repeat expansion (CTG18.1) in the transcription factor 4 (TCF4) gene is estimated to account for two thirds of FECD cases. There is a high degree of similarity between the transcriptomic profiles with (RE+) and without (RE-) the expansion. The molecular mechanisms of FECD and the difference between the two FECD types remain to be elucidated.
METHOD: Analyses were based on publicly available RNA sequencing datasets of human corneal endothelial tissues. We compared the distributions of differentially expressed genes between the RE+ and RE- transcriptomic profiles for a given co-expression network module. Upstream regulator analysis, alternative splicing analysis, motif enrichment analysis, and structure prediction were conducted.
RESULTS: The expression levels of ribonucleic acid binding motif protein 20 (RBM20) were upregulated in both RE+ cases and RE+ controls. Consistently, its motif was enriched in the skipped exon events of RE+ subjects compared with RE- subjects. There were skipped exon events in three genes-DST, FNBP1 and SORBS1- consistently identified in RE+ subjects out of the documented RBM20 target genes in the literature.
CONCLUSION: RBM20 may represent an RE+ specific factor in the pathogenesis of FECD. The increase of RBM20 expression in RE+ individuals may contribute to the disease by repressing the inclusion of exons.
METHOD: Analyses were based on publicly available RNA sequencing datasets of human corneal endothelial tissues. We compared the distributions of differentially expressed genes between the RE+ and RE- transcriptomic profiles for a given co-expression network module. Upstream regulator analysis, alternative splicing analysis, motif enrichment analysis, and structure prediction were conducted.
RESULTS: The expression levels of ribonucleic acid binding motif protein 20 (RBM20) were upregulated in both RE+ cases and RE+ controls. Consistently, its motif was enriched in the skipped exon events of RE+ subjects compared with RE- subjects. There were skipped exon events in three genes-DST, FNBP1 and SORBS1- consistently identified in RE+ subjects out of the documented RBM20 target genes in the literature.
CONCLUSION: RBM20 may represent an RE+ specific factor in the pathogenesis of FECD. The increase of RBM20 expression in RE+ individuals may contribute to the disease by repressing the inclusion of exons.