DDX24 Mutation Alters NPM1 Phase Behavior and Disrupts Nucleolar Homeostasis in Vascular Malformations
Haopei Zhang, Qiuyue Chen, Qianqian Zhang, Hairun Gan, Hanjie Li, Shoudeng Chen, Shan Hong, Pengfei Pang, Huanhuan He
Abstract
, partitioned less into the nucleoli in tissues from patients with MOVLD syndrome and cultured endothelial cells (ECs), altering nucleolar morphology. Furthermore, DDX24 was directly associated with NPM1 to regulate its phase behavior as a client in the nucleolar granular component (GC). Functionally, we showed that DDX24 was essential in maintaining nucleolar homeostasis of ECs and that either mutation or knockdown of DDX24 led to the dysfunction of ribosome biogenesis and the elevated capability of cell migration and tube formation. Our findings illustrate how DDX24 mutation affects nucleolar structure and function by regulating the phase behavior of NPM1 in the setting of vascular malformation.