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The RNA-binding protein HuR is a negative regulator in adipogenesis

Author

Listed:
  • Diana Teh Chee Siang

    (Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School)

  • Yen Ching Lim

    (Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School)

  • Aung Maung Maung Kyaw

    (Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School)

  • Khaing Nwe Win

    (Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School)

  • Sook Yoong Chia

    (Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School)

  • Ufuk Degirmenci

    (Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School)

  • Xiang Hu

    (Departments of Endocrine and Metabolic Diseases, The first Affiliated Hospital of Wenzhou Medical University)

  • Bryan C. Tan

    (Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School)

  • Arcinas Camille Esther Walet

    (Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School)

  • Lei Sun

    (Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School
    Institute of Molecular and Cell Biology)

  • Dan Xu

    (Cardiovascular and Metabolic Disorders Program, Duke-NUS Medical School)

Abstract

Human antigen R (HuR) is an essential regulator of RNA metabolism, but its function in metabolism remains unclear. This study identifies HuR as a major repressor during adipogenesis. Knockdown and overexpression of HuR in primary adipocyte culture enhances and inhibits adipogenesis in vitro, respectively. Fat-specific knockout of HuR significantly enhances adipogenic gene program in adipose tissues, accompanied by a systemic glucose intolerance and insulin resistance. HuR knockout also results in depot-specific phenotypes: it can repress myogenesis program in brown fat, enhance inflammation program in epidydimal white fat and induce browning program in inguinal white fat. Mechanistically, HuR may inhibit adipogenesis by recognizing and modulating the stability of hundreds of adipocyte transcripts including Insig1, a negative regulator during adipogenesis. Taken together, our work establishes HuR as an important posttranscriptional regulator of adipogenesis and provides insights into how RNA processing contributes to adipocyte development.

Suggested Citation

  • Diana Teh Chee Siang & Yen Ching Lim & Aung Maung Maung Kyaw & Khaing Nwe Win & Sook Yoong Chia & Ufuk Degirmenci & Xiang Hu & Bryan C. Tan & Arcinas Camille Esther Walet & Lei Sun & Dan Xu, 2020. "The RNA-binding protein HuR is a negative regulator in adipogenesis," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-14001-8
    DOI: 10.1038/s41467-019-14001-8
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