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bioRxiv · 10.64898/2026.02.19.706916

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

Fairchild, D.·Semenova, I. V.·Geddes-Buehre, D.·Li, Y.·Szczepaniak, R.·Weller, S. K.·Hao, B.·Bezsonova, I.
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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.

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Fairchild, D., Semenova, I. V., Geddes-Buehre, D., Li, Y., Szczepaniak, R., Weller, S. K., Hao, B., Bezsonova, I.. 2026-02-20. PXL: a Nucleic Acid-Binding Module of Promyelocytic Leukemia Protein. https://doi.org/10.64898/2026.02.19.706916

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