Multi-omics analysis reveals NSUN2-mediated m5C methylation of DOCK9 regulating vascular stability in brain arteriovenous malformations - PubMed
5 hours ago
- #vascular biology
- #neurovascular disorders
- #RNA methylation
- Multi-omics analysis identifies NSUN2-mediated m5C methylation of DOCK9 as a regulator of vascular stability in brain arteriovenous malformations (bAVMs).
- DOCK9, an endothelial-specific gene regulated by m5C methylation, is downregulated in ruptured bAVMs.
- Functional assays and CRISPR-Cas9 zebrafish models demonstrate DOCK9's role in endothelial proliferation, migration, and vascular integrity.
- Endothelial-specific overexpression of dock9 rescues vascular defects in dock9-deficient zebrafish.
- NSUN2 methyltransferase binds and methylates DOCK9 mRNA to stabilize its expression; NSUN2 knockdown mimics dock9 deficiency.
- The NSUN2-DOCK9 axis links m5C dysregulation to cerebrovascular instability and bAVM rupture, suggesting a potential therapeutic target.