2. Academic Validation
  3. Cytoplasmic PXR regulates glucose metabolism by binding mRNAs and modulating their stability

Cytoplasmic PXR regulates glucose metabolism by binding mRNAs and modulating their stability

  • Nat Struct Mol Biol. 2025 Aug 12. doi: 10.1038/s41594-025-01614-5.
Xiaofei Wang 1,  Zehua Wang 1,  Sihan Li 1,  Dhamotharan Pattarayan 1,  Yifei Wang 1,  Jingchen Zhai 2,  Yu Zhang 1,  Haolin Wang 1,  Meishu Xu 1,  Junjie Zhu 1,  Junmei Wang 2,  Xiaochao Ma 1,  Sridhar Mani 3,  Wen Xie 1,  Min Zhang 4,  Da Yang 5 6 7
Affiliations

Affiliations

  • 1 Center for Pharmacogenetics, Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA, USA.
  • 2 Department of Pharmaceutical Sciences and Computational Chemical Genomics Screening Center, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA, USA.
  • 3 Department of Medicine, Oncology, Molecular Pharmacology, and Genetics, Albert Einstein College of Medicine, Bronx, NY, USA.
  • 4 Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA, USA. miz45@pitt.edu.
  • 5 Center for Pharmacogenetics, Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA, USA. dyang@pitt.edu.
  • 6 UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA. dyang@pitt.edu.
  • 7 Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, PA, USA. dyang@pitt.edu.
PMID: 40797049 DOI: 10.1038/s41594-025-01614-5
Abstract

Pregnane X receptor (PXR) is a nuclear receptor considered to be a master transcription factor of xenobiotic metabolism. Here, using enhanced ultraviolet crosslinking and immunoprecipitation, we show that PXR can bind mRNAs in different Cancer cell lines and normal liver tissues. PXR-bound mRNAs include genes related to metabolic reprogramming and lipid metabolism. Separately from its known nuclear transcriptional function, cytoplasmic PXR binds and stabilizes mature mRNA containing C+G-enriched sequences through its zinc-finger domain. Mechanistically, cytoplasmic PXR interacts with RNH1, an RNase Inhibitor, to regulate RNA stability. In colorectal Cancer cells, cytoplasmic PXR facilitates glucose uptake by stabilizing SLC2A1 mRNA. This process further promotes cell proliferation and Cancer development. Our study unveils a previously unknown dimension of PXR-mediated gene regulation by characterizing PXR as an RNA-binding protein important for mRNA stability in the cytoplasm.

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Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-124830
    ≥99.0%, hPXR Antagonist