Loss of the long non-coding RNA OIP5-AS1 exacerbates heart failure in a sex-specific manner
journal contributionposted on 2021-07-27, 06:25 authored by A Zhuang, AC Calkin, S Lau, H Kiriazis, DG Donner, Y Liu, ST Bond, SC Moody, EAM Gould, TD Colgan, SR Carmona, Michael InouyeMichael Inouye, TQ de Aguiar Vallim, EJ Tarling, GA Quaife-Ryan, JE Hudson, ER Porrello, P Gregorevic, XM Gao, XJ Du, Julie McMullenJulie McMullen, BG Drew
Long non-coding RNAs (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 uncharacterized. 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 knockout (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 wild-type 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.