학술논문
Loss of the long non-coding RNA OIP5-AS1 exacerbates heart failure in a sex-specific manner
Document Type
article
Author
Aowen Zhuang; Anna C. Calkin; Shannen Lau; Helen Kiriazis; Daniel G. Donner; Yingying Liu; Simon T. Bond; Sarah C. Moody; Eleanor A.M. Gould; Timothy D. Colgan; Sergio Ruiz Carmona; Michael Inouye; Thomas Q. de Aguiar Vallim; Elizabeth J. Tarling; Gregory A. Quaife-Ryan; James E. Hudson; Enzo R. Porrello; Paul Gregorevic; Xiao-Ming Gao; Xiao-Jun Du; Julie R. McMullen; Brian G. Drew
Source
iScience, Vol 24, Iss 6, Pp 102537- (2021)
Subject
Language
English
ISSN
2589-0042
Abstract
Summary: 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.