NTRAS hnRNPL RNA sequencing in HUVECs. NTRAS hnRNPL RNA sequencing in HUVECs

In the current project with aim to unequivocally characterize a novel splicing-regulatory network that proves to be a central mediator of endothelial barrier function and vascular integrity. At the core of this network is the endothelial enriched lncRNA NTRAS (annotated as RP11-354k1.1) is shown to control alternative splicing decisions in HUVECs through interplaying with splicing factor hnRNPL. Specifically, in the project we show that NTRAS sequesters the splicing factor hnRNPL through a CA dinucleotide motif, to enhance TJP1 exon 20 usage, thereby TJP1α+ isoform. In turn disrupting TJP1α+ isoform expression impaired endothelial barrier function. Collectively, this splicing-regulatory network might prove fundamental in unlocking new interventions strategic to prevent or reverse vascular leakage.