Identification of a novel nuclease activity in human DDX49 helicase
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 (<i>DDX49</i> <sup>+/-</sup>) U2OS cell line is defective at cell migration, a phenotype supporting the association of DDX49 with cancer cell invasiveness. Measurement of RNAs in <i>DDX49</i> <sup>+/-</sup> indicates that DDX49 is required to sustain levels of 5.8S rRNA.
Authors
- Tom Killelea (ORCID: https://orcid.org/0000-0003-0974-8034)
- Edward L. Bolt (ORCID: https://orcid.org/0000-0002-5656-7706)
- Ashley J. Parkes (ORCID: https://orcid.org/0000-0003-1678-6039)
- Anna Lou‐Hing (ORCID: https://orcid.org/0009-0007-0543-8529)
- Louise Martin
- Sabesan Anandavijayan
- Olivia Downs (ORCID: https://orcid.org/0000-0002-0487-9783)
- Fiorela Kapllanaj
Institutions
- University of Nottingham (GB)
Publication Details
- Journal
- Royal Society Open Science
- Published
- 2024-12-01
- DOI
- https://doi.org/10.1098/rsos.241891
- Primary Topic
- CRISPR and Genetic Engineering
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Biotechnology and Biological Sciences Research Council