Work

MDV-encoded protein kinase US3 phosphorylates WTAP to inhibit transcriptomic m6A modification and cellular protein translation

Year: 2024

Type: article

Abstract: Marek’s disease virus (MDV)-encoded U S 3 is a highly conserved serine/threonine protein kinase in alpha-herpesviruses. In other alpha-herpesviruses, such as pseudorabies virus (PRV), U S 3 phosphorylates the N6-methyladenosine (m 6 A) methyltransferase Wilms tumor 1-associated protein (WTAP), inhibiting m 6 A modification. However, the role and mechanism of U S 3-mediated WTAP phosphorylation during MDV infection remain undefined. Our study revealed that MDV infection in vitro does not alter WTAP expression , while significant changes in WTAP expression occur during the MDV life cycle in vivo. We demonstrated that MDV-encoded U S 3 interacts with and co-localizes with WTAP in the nucleus. Further analysis showed that U S 3 binds to WTAP's C-terminal domain and phosphorylates WTAP at S273, S305, S314, and S375. Notably, the interaction between U S 3 and WTAP does not affect WTAP stability but inhibits transcriptomic m 6 A modification and cellular protein translation . Therefore, these findings enhance our understanding of the molecular mechanisms underlying MDV infection.

Source: Veterinary Microbiology

DOI: 10.1016/j.vetmic.2024.110335