Abstract:
:Long non-coding RNAs (lncRNAs) contribute to cardiac (patho)physiology. Aging is the major risk factor for cardiovascular disease with cardiomyocyte apoptosis as one underlying cause. Here, we report the identification of the aging-regulated lncRNA Sarrah (ENSMUST00000140003) that is anti-apoptotic in cardiomyocytes. Importantly, loss of SARRAH (OXCT1-AS1) in human engineered heart tissue results in impaired contractile force development. SARRAH directly binds to the promoters of genes downregulated after SARRAH silencing via RNA-DNA triple helix formation and cardiomyocytes lacking the triple helix forming domain of Sarrah show an increase in apoptosis. One of the direct SARRAH targets is NRF2, and restoration of NRF2 levels after SARRAH silencing partially rescues the reduction in cell viability. Overexpression of Sarrah in mice shows better recovery of cardiac contractile function after AMI compared to control mice. In summary, we identified the anti-apoptotic evolutionary conserved lncRNA Sarrah, which is downregulated by aging, as a regulator of cardiomyocyte survival.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Trembinski DJ,Bink DI,Theodorou K,Sommer J,Fischer A,van Bergen A,Kuo CC,Costa IG,Schürmann C,Leisegang MS,Brandes RP,Alekseeva T,Brill B,Wietelmann A,Johnson CN,Spring-Connell A,Kaulich M,Werfel S,Engelhardt S,Hirtdoi
10.1038/s41467-020-15995-2subject
Has Abstractpub_date
2020-04-27 00:00:00pages
2039issue
1issn
2041-1723pii
10.1038/s41467-020-15995-2journal_volume
11pub_type
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