Splice Variants of LncRNA RNA ANRIL Exert Opposing Effects on Endothelial Cell Activities Associated with Coronary Artery Disease

Each gene typically has multiple alternatively spliced transcripts. Different transcripts are assumed to play a similar biological role; however, some transcripts may simply lose their function due to loss of important functional domains. Here, we show that two different transcripts of lncRNA gene associated with coronary artery disease (CAD) play antagonizing roles against each other. We previously reported that , the short transcript, is downregulated in coronary arteries from CAD patients, and reduces monocyte adhesion to endothelial cells (ECs) and transendothelial monocyte migration (TEM). Interestingly, the longest transcript is significantly upregulated in coronary arteries from CAD patients. Overexpression of transcript increases monocyte adhesion to ECs and TEM, whereas knockdown of expression reduces monocyte adhesion to ECs and TEM. Much more dramatic effects were observed for the combination of overexpression of and knockdown of or the combination of knockdown of and overexpression of . The antagonizing effects of transcripts and were associated with their opposite effects on expression of downstream target genes or . Our results demonstrate that different transcripts of lncRNA can exert antagonizing effects on biological functions, thereby providing important insights into the biology of lncRNA. The data further support the hypothesis that is the causative gene at the 9p21 CAD susceptibility locus.