Scholarlink

<p>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 <i>SLC2A1</i> 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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 发表日期：

    2025年8月12日

查看全文
  • Xiaofei Wang,
  • Zehua Wang,
  • Sihan Li,
  • Dhamotharan Pattarayan,
  • Yifei Wang,
  • Jingchen Zhai,
  • Yu Zhang,
  • Haolin Wang,
  • Meishu Xu,
  • Junjie Zhu,
  • Junmei Wang,
  • Xiaochao Ma,
  • Sridhar Mani,
  • Wen Xie,
  • Min Zhang,
  • Da Yang

摘要

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.