Authors
Daniel Fairchild, Irina V Semenova, Dane Geddes-Buehre, Yunfeng Li, Renata Szczepaniak, Sandra K Weller, Bing Hao, Irina Bezsonova
Published in
Nucleic acids research. Volume 54. Issue 19. Oct 13, 2026.
Abstract
The promyelocytic leukemia protein (PML) is a stress-response factor that assembles into PML nuclear bodies, dynamic subnuclear compartments involved in tumor suppression and antiviral defense. The most abundant isoform, PML-1, has been linked to transcriptional regulation, genome stability, and antiviral responses, yet the molecular basis of these functions remains unclear and is generally attributed to proteins associated with PML nuclear bodies. Here, we report that PML-1 itself harbors a previously structurally uncharacterized nucleic acid-binding domain. The domain, termed PXL, is encoded by exon 9 of the PML gene and is unique to isoform 1. Its structure reveals an exonuclease III fold, but lacks the catalytic residues required for activity, defining PXL as a pseudo-exonuclease. Biochemical, structural, mutational, and cellular analyses demonstrate that PXL specifically binds G-rich oligonucleotides implicated in G-quadruplex formation and displays a strong in vitro preference for polyUG RNA. Furthermore, deletion of the PXL domain significantly decreases PML colocalization with G-quadruplexes in cells, downregulates genomic maintenance pathways, and modulates the expression of E2F target and interferon-α response genes. These findings provide a molecular basis for previous observations implicating PML in nucleic acid-associated functions and establish a mechanistic framework for future studies of PML-mediated stress responses, nuclear organization, and gene regulation.
PMID:
42866950
Bibliographic data and abstract were imported from PubMed on 14 Oct 2026.
Read full publication at:
Please sign in
to see all details.
Advertisement
Stats
- Recommendations n/a n/a positive of 0 vote(s)
- Views 4
- Comments 0