Identification of a novel nuclease activity in human DDX49 helicase

Parkes, Ashley J.; Anandavijayan, Sabesan; Lou-Hing, Anna; Downs, Olivia; Killelea, Tom; Martin, Louise; Kapllanaj, Fiorela; Bolt, Edward L.

Abstract

Human DDX49 is an emerging target in cancer progression and retroviral diseases through its essential roles in nucleolar RNA processing. Here, we identify nuclease activity of human DDX49, which requires active site aspartate residues within a conserved region of metazoan DDX49s that is absent from yeast and archaeal DDX49 homologues. We provide evidence that DDX49 nuclease activity is facilitated by its helicase activity. Using CRISPR-Cas9 genetic editing, we show that a heterozygous (DDX49+/−) U2OS cell line is defective at cell migration, a phenotype supporting the association of DDX49 with cancer cell invasiveness. Measurement of RNAs in DDX49+/− indicates that DDX49 is required to sustain levels of 5.8S rRNA.

Citation

Parkes, A. J., Anandavijayan, S., Lou-Hing, A., Downs, O., Killelea, T., Martin, L., Kapllanaj, F., & Bolt, E. L. (2024). Identification of a novel nuclease activity in human DDX49 helicase. Royal Society Open Science, 11(12), Article 241891. https://doi.org/10.1098/rsos.241891

• Journal Article Type: Article
• Acceptance Date: Nov 8, 2024
• Online Publication Date: Dec 18, 2024
• Publication Date: 2024-12
• Deposit Date: Feb 24, 2025
• Publicly Available Date: Feb 24, 2025
• Electronic ISSN: 2054-5703
• Publisher: The Royal Society
• Peer Reviewed: Peer Reviewed
• Volume: 11
• Issue: 12
• Article Number: 241891
• DOI: https://doi.org/10.1098/rsos.241891
• Public URL: https://nottingham-repository.worktribe.com/output/42812882
• Publisher URL: https://royalsocietypublishing.org/doi/10.1098/rsos.241891