Related Experiment Video
Updated: Mar 25, 2026
Isolation of Murine Retinal Endothelial Cells for Next-Generation Sequencing
Published on: October 11, 2021
Multi-omics analysis reveals NSUN2-mediated m5C methylation of DOCK9 regulating vascular stability in brain
Ganglei Li1, Hongfei Zhang1, Biyun Wang2
1Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai 200040, China; National Center for Neurological Disorders, Shanghai, China; Shanghai Key Laboratory of Brain Function and Restoration and Neural Regeneration, Shanghai, China; Neurosurgical Institute of Fudan University, Shanghai, China; Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China.
Abstract:
RNA 5-methylcytosine (m5C) methylation is a key post-transcriptional modification, yet its role in vascular stability remains unclear. Through integrative m5C-RNA immunoprecipitation and transcriptomic, proteomic, and single-cell analyses of ruptured and unruptured human brain arteriovenous malformations (bAVMs), we find DOCK9 to be an endothelial-specific, m5C-regulated gene downregulated in the ruptured group. Functional assays in endothelial cells and CRISPR-Cas9 zebrafish models show that DOCK9 controls endothelial proliferation, migration, and vascular integrity. Endothelial-specific overexpression of dock9 rescues vascular defects in dock9-deficient zebrafish. Mechanistically, the RNA methyltransferase NSUN2 directly binds and methylates DOCK9 mRNA to stabilize its expression. NSUN2 knockdown mimics dock9 deficiency in zebrafish, supporting a functional NSUN2-DOCK9 axis. These findings show a molecular pathway linking m5C dysregulation to cerebrovascular instability and bAVM rupture. Targeting this axis may offer a strategy for stabilizing fragile cerebrovascular lesions.
Related Concept Videos
01:24Regulation of Angiogenesis and Blood Supply
01:10Mechanism of Angiogenesis
03:14Notch Signaling Pathway
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...