The Cardiomyocyte RNA-Binding Proteome: Links to Intermediary Metabolism and Heart Disease

RNA functions through the dynamic formation of complexes with RNA-binding proteins (RBPs) in all clades of life. We determined the RBP repertoire of beating cardiomyocytic HL-1 cells by jointly employing two in vivo proteomic methods, mRNA interactome capture and RBDmap. Together, these yielded 1,148 RBPs, 391 of which are shared with all other available mammalian RBP repertoires, while 393 are thus far unique to cardiomyocytes. RBDmap further identified 568 regions of RNA contact within 368 RBPs. The cardiomyocyte mRNA interactome composition reflects their unique biology. Proteins with roles in cardiovascular physiology or disease, mitochondrial function, and intermediary metabolism are all highly represented. Notably, we identified 73 metabolic enzymes as RBPs. RNA-enzyme contacts frequently involve Rossmann fold domains with examples in evidence of both, mutual exclusivity of, or compatibility between RNA binding and enzymatic function. Our findings raise the prospect of previously hidden RNA-mediated regulatory interactions among cardiomyocyte gene expression, physiology, and metabolism. [Display omitted] •mRNA interactome capture and RBDmap reveal the cardiomyocyte RNA-binding proteome•1,148 RBPs are identified, 393 of which are thus far unique to cardiomyocytes•Many cardiac RBPs have links to heart disease and mitochondrial metabolism•Contacts of metabolic enzymes with RNA frequently involve Rossmann fold domains RNA functions through dynamic interactions with RNA-binding proteins (RBPs) in all clades of life. In this article, Liao et al. present the RBP repertoire of murine cardiomyocytes. Their findings reflect the unique cardiomyocyte biology and raise the prospect of previously hidden RNA-mediated regulatory interactions between gene expression, physiology, and metabolism.