Fig. 1. Sarrahis an evolutionary conserved, anti-apoptotic lncRNA in cardiomyocytes downregulated during aging.

a Two different siRNAs against each of the 76 cardiomyocyte-enriched lncRNAs from Supplementary Fig. 1c were transfected in HL-1 cells (n = 3), the average for both is displayed. The lncRNA highlighted in red corresponds to lncRNA Sarrah. Apoptosis levels were determined in standard cell culture conditions or after induction with 100 µM H₂O₂ by measuring caspase-3/7 activity. b The genomic Sarrah locus overlaps with the OXCT1 gene encoding SCOT1. Its transcription start site lies within the first OXCT1 intron. c Three different cell types (cardiomyocytes (CM), endothelial cells (EC) and fibroblasts (FB)) were isolated from the hearts of 12-week-old mice. RNA was isolated and Sarrah levels were determined by qRT-PCR (n = 5; SEM). d Sarrah downregulation during aging was confirmed by qRT-PCR with RNA from total young and aged mouse heart tissue (n = 6; SEM; ***t-test p = 0.00005). e Caspase-3/7 activity was measured in GapmeR-transfected mouse (HL-1 cell line) and human (primary cells) cardiomyocytes to confirm the increase in apoptosis upon Sarrah knockdown (HL-1: n = 3; SEM; ***p = 0.0001); hCM: n = 6; SEM; *t-test p = 0.0486). f Caspase-3/7 activity was measured in SARRAH overexpressing primary human cardiomyocytes (n = 4; SEM; *t-test p = 0.0286).