High expression of the underexplored SLC4A11 protein-coding transcript is specific to the corneal endothelium

Abstract

Abstract Fuchs’ endothelial corneal dystrophy (FECD) and congenital hereditary endothelial dystrophy (CHED) are corneal endothelial pathologies associated with SLC4A11 gene variants. The principal findings on the expression and function of SLC4A11 in the corneal endothelium have been based on studies of three major transcripts variants (v1, v2 and v3) and their protein products. We aimed to address gaps and resolve contradictions regarding the expression of SLC4A11 . Our transcriptomic analysis revealed predominant expression of RefSeq-annotated protein-coding transcripts v6 and v3, but not v2 and v1, in the corneal endothelium of patients with FECD and controls. We also demonstrated the specificity of high SLC4A11 and major transcript expression to corneal endothelium. Using the 5’ RACE method, we directly showed that the major transcription start site is at the beginning of v6, from which v3 with an extended 5’UTR is also transcribed. We estimated the fraction of v6 and v3 from the overall expression as 0.63 and 0.34, respectively. We also obtained evidence of full-length v6 expression in corneal endothelium and its ability to drive translation of the previously described v2M36 protein isoform. These findings provide new information on SLC4A11 gene expression and functional consequences of some genomic variants identified in patients with FECD.