Journal
ISCIENCE
Volume 24, Issue 6, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.isci.2021.102537
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Funding
- Victorian State Government OIS program
- National Health & Medical Research Council (NHMRC) of Australia [APP1127336]
- National Heart Foundation of Australia, via the Future Leader Fellowship Scheme [101789, 100067]
- NHMRC [APP1078985, APP1117835]
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The study demonstrates the significant role of OIP5-AS1 in cardiac development and disease, with knockout of this gene leading to exacerbated heart failure in female mice. RNA-sequencing results suggest that OIP5-AS1 regulates pathways impacting mitochondrial function.
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.
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