Loss of the Long Non-coding RNA OIP5-AS1 Exacerbates Heart Failure in a Sex-Specific Manner.

Summary Long ncRNAs (lncRNAs) have been demonstrated to influence numerous biological processes, being strongly implicated in the maintenance and physiological function of various tissues including the heart. The lncRNA OIP5-AS1 (1700020I14Rik/Cyrano) has been studied in several settings, however its role in cardiac pathologies remains mostly uncharacterised. Using a series of in vitro and ex vivo methods we demonstrate that OIP5-AS1 is regulated during cardiac development in rodent and human models, and in disease settings in mice. Using CRISPR, we engineered a global OIP5-AS1 knock out (KO) mouse and demonstrated that female KO mice develop exacerbated heart failure following cardiac pressure overload (transverse aortic constriction - TAC), but male mice do not. RNA-sequencing of WT and KO hearts suggest that OIP5-AS1 regulates pathways that impact mitochondrial function. Thus, these findings highlight OIP5-AS1 as a gene of interest in sex-specific differences in mitochondrial function and development of heart failure.