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

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journal contribution
posted on 27.07.2021, 06:25 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 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.

History

Publication Date

25/06/2021

Journal

iScience

Volume

24

Issue

6

Article Number

102537

Pagination

(p. 102537-102537)

Publisher

Elsevier BV

ISSN

2589-0042

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The Author reserves all moral rights over the deposited text and must be credited if any re-use occurs. Documents deposited in OPAL are the Open Access versions of outputs published elsewhere. Changes resulting from the publishing process may therefore not be reflected in this document. The final published version may be obtained via the publisher’s DOI. Please note that additional copyright and access restrictions may apply to the published version.

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