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 DuJulie R. McMullen, Brian G. Drew

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3 Citations (Scopus)

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.

Original languageEnglish
Article number102537
Number of pages19
JournaliScience
Volume24
Issue number6
DOIs
Publication statusPublished - 25 Jun 2021

Keywords

  • Cardiovascular medicine
  • Molecular physiology
  • Transcriptomics

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