DDX24 modulates angiogenesis by promoting CCR4-NOT complex-dependent mRNA decay

DEAD-box (DDX) RNA helicases play critical roles in gene regulation by interacting with RNAs and influencing RNA fate and function. Our previous study associated DDX24 dysfunction with vascular development, but its precise role in RNA metabolism in the context of angiogenesis remains unclear. Here, we identified DDX24-bound messenger RNAs (mRNAs) in endothelial cells using infrared cross-linking immunoprecipitation sequencing. We found that DDX24 modulates endothelial cell functions by directly binding to and regulating specific mRNA targets that are crucial for vascular development and angiogenesis, such as CLEC14A and ERG. Mechanistically, DDX24 promotes the decay of these mRNA targets in a CCR4-NOT deadenylase complex-dependent manner. These results establish a link between DDX24-dependent regulation of mRNA stability and endothelial cell function, providing novel therapeutic targets for angiogenesis-related diseases.