Loss of the long non-coding RNA OIP5-AS1 exacerbates heart failure in a sex-specific manner

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

doi:10.1016/j.isci.2021.102537

Loss of the long non-coding RNA OIP5-AS1 exacerbates heart failure in a sex-specific manner

iScience. 2021 May 13;24(6):102537. doi: 10.1016/j.isci.2021.102537. eCollection 2021 Jun 25.

Authors

Aowen Zhuang^{1

2}, Anna C Calkin^{1

2}, Shannen Lau¹, Helen Kiriazis¹, Daniel G Donner¹, Yingying Liu¹, Simon T Bond¹, Sarah C Moody¹, Eleanor A M Gould¹, Timothy D Colgan¹, Sergio Ruiz Carmona¹, Michael Inouye^{1

3}, Thomas Q de Aguiar Vallim⁴, Elizabeth J Tarling⁴, Gregory A Quaife-Ryan⁵, James E Hudson⁵, Enzo R Porrello^{6

7}, Paul Gregorevic^{1

7}, Xiao-Ming Gao¹, Xiao-Jun Du¹, Julie R McMullen^{1

2}, Brian G Drew^{1

2}

Affiliations

¹ Baker Heart & Diabetes Institute, Melbourne, VIC 3004, Australia.
² Central Clinical School, Monash University, Melbourne, VIC 3004, Australia.
³ Department of Public Health and Primary Care, University of Cambridge, Cambridge, CB1 8RN, UK.
⁴ Department of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
⁵ QIMR Berghofer, Brisbane, QLD 4072, Australia.
⁶ Murdoch Children's Research Institute, Parkville, VIC 3052, Australia.
⁷ Centre for Muscle Research, Department of Anatomy and Physiology, School of Biomedical Sciences, University of Melbourne, Parkville, VIC 3010, Australia.

Abstract

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.

Keywords: Cardiovascular medicine; Molecular physiology; Transcriptomics.

Associated data

figshare/10.6084/m9.figshare.14538537