PXL: a Nucleic Acid-Binding Module of Promyelocytic Leukemia Protein

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. Here, we report that PML-1 contains a unique nucleic acid- binding module, PXL, and determine its three-dimensional structure by X-ray crystallography. Further biochemical, mutational, and cellular analyses, including RNA-seq, demonstrate that this module selectively binds single-stranded G-rich RNA and DNA motifs and modulates the transcriptome. These findings reveal an unexpected molecular function of PML and provide a framework for understanding its roles in nuclear organization and gene regulation.