Aging-regulated anti-apoptotic long non-coding RNA Sarrah augments recovery from acute myocardial infarction

Nat Commun. 2020 Apr 27;11(1):2039. doi: 10.1038/s41467-020-15995-2.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aging
  • Animals
  • Apoptosis*
  • Carrier Proteins / genetics
  • Cell Survival
  • Coenzyme A-Transferases / genetics
  • Disease Models, Animal
  • Gene Silencing
  • Humans
  • LIM Domain Proteins / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myocardial Infarction / genetics*
  • Myocytes, Cardiac / cytology*
  • NF-E2-Related Factor 2 / genetics
  • RNA, Antisense / genetics
  • RNA, Long Noncoding / genetics*
  • RNA, Small Interfering / genetics
  • p300-CBP Transcription Factors / genetics


  • Carrier Proteins
  • Crip2 protein, mouse
  • LIM Domain Proteins
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • RNA, Antisense
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • p300-CBP Transcription Factors
  • Coenzyme A-Transferases
  • 3-ketoacid CoA-transferase