Page 31 - IBRO_RNA School_Abstract Book

Long Non-Coding RNA Based Regulation of Endothelial

Cells

Sridhar Sivasubbu

CSIR-Institute of Genomics and Integrative Biology,

Mathura Road, Delhi, India

Controlled endothelial cell permeability is an attribute of vascular homeostasis and
maintenance. Long non coding RNAs (lncRNAs) are emerging as regulators of
endothelial function with potential to act as biomarkers, drug targets or biological

substitutes. A Vascular Endothelial Associated Long non-coding RNA (VEAL) was
identified using cell-type-specific RNA sequencing from zebrafish endothelial cells.
TALEN-mediated editing of the genomic locus of VEAL resulted in defects charac-
terized by vascular integrity leading to cranial hemorrhage in zebrafish mutant em-
bryos. We identified Protein kinase C-beta b as a direct interacting partner of VEAL.
Using Protein kinase C-beta (PRKCB) as bait, the human counterpart of VEAL was
also isolated. Using a combination of classical zebrafish genetics, cell biology
exper-iments and molecular simulation studies we demonstrate a novel intrinsic
lncRNA based-regulation of PRKCB activity wherein VEAL acts as a competitor to

the PRK-CB activator Diacylglycerol for modulating endothelial cell permeability.
This study adds a conserved lncRNA-mediated regulatory angle to the PRKCB arm
of endo-thelial cell pathways and provides a novel handle for drug targeting and/or
augmen-tation of existing therapies for managing endothelial hyperpermeability.