TGF-b regulated RNA-binding proteins control endothelial function and mesenchymal transition in cardiac endothelial cells. Mus musculus

Endothelial to mesenchymal transition (EndoMT) plays a key role in heart development, but is also implicated in cardiovascular diseases in postnatal life. While the roles of TGF-b as inducer of EndoMT on the transcriptional level are well characterised, its post-transcriptional regulatory mechanisms remain largely unknown. Here, we identified global TGF-b stimulated changes in the endothelial mRNA interactome using RNA interactome capture. Characterisation of TGF-b regulated RNA binding proteins (RBPs) revealed heterogeneous nuclear ribonucleoprotein H1 (hnRNP H1) and Cold Shock Domain Containing E1 (Csde1) as key regulators of endothelial function and EndoMT. We profiled TGF-b driven changes in the RNA binding patterns of hnRNP H1 and Csde1, finding that they dynamically bind and regulate specific subsets of functionally connected RNAs related to mesenchymal activation. Together, we show that RBPs play a key role in EndoMT and that the RBPs hnRNP H1 and Csde1 maintain endothelial cell function and counteract mesenchymal activation.