Abstract
Aberrant synthesis of mitochondrial proteins impairs cardiac function and causes heart disease. However, the mechanism of regulation of mitochondria encoded protein expression during cardiac disease remains underexplored. Here, we have shown that multiple pathogenic cardiac stressors induce the expression of miR-574 guide and passenger strands (miR-574-5p/3p) in both humans and mice. miR-574 knockout mice exhibit severe cardiac disorder under heart disease-triggering stresses. miR-574-5p/3p mimics that are delivered systematically using nanoparticles reduce cardiac pathogenesis under disease insults. Transcriptome analysis of miR-574-null hearts uncovers FAM210A as a common target mRNA for both strands of miR-574. The interactome capture and translational state analyses suggest that FAM210A interacts with mitochondrial translation factors and regulates the protein expression of mitochondrial encoded electron transport chain genes. Using a human cardiomyocyte cell culture system, we discover that miR-574 regulates FAM210A expression and modulates mitochondrial encoded protein expression, which influences cardiac remodeling in heart failure.
Footnotes
Abbreviations of key terms: ACM, adult cardiomyocytes; CF, cardiac fibroblasts; CM, cardiomyocytes; ETC, electron transport chain; FAM210A, family with sequence similarity 210 member A; HF, heart failure; ISO, isoproterenol; MEG, mitochondrial encoded gene; MI, myocardial infarction; NEMG, nuclear-encoded mitochondrial gene; RBP, RNA-binding protein; RISC, RNA-induced silencing complex; TAC, transverse aortic constriction; UTR, untranslated region
