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Identification of a subnuclear body involved in sequence-specific cytokine RNA processing

Author

Listed:
  • Sungwook Lee

    (College of Life Science and Biotechnology, Yonsei University)

  • Taeyun A. Lee

    (College of Life Science and Biotechnology, Yonsei University)

  • Eunhye Lee

    (College of Life Science and Biotechnology, Yonsei University)

  • Sujin Kang

    (College of Life Science and Biotechnology, Yonsei University)

  • Areum Park

    (College of Life Science and Biotechnology, Yonsei University)

  • Seung Won Kim

    (Yonsei University College of Medicine
    Severance Biomedical Science Institute, Yonsei University College of Medicine)

  • Hyo Jin Park

    (College of Life Science and Biotechnology, Yonsei University)

  • Je-Hyun Yoon

    (Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH)

  • Sang-Jun Ha

    (College of Life Science and Biotechnology, Yonsei University)

  • Taesun Park

    (College of Human Ecology, Yonsei University)

  • Ju-Seog Lee

    (University of Texas MD Anderson Cancer Center)

  • Jae Hee Cheon

    (Yonsei University College of Medicine
    Severance Biomedical Science Institute, Yonsei University College of Medicine)

  • Boyoun Park

    (College of Life Science and Biotechnology, Yonsei University)

Abstract

Processing of interleukin RNAs must be tightly controlled during the immune response. Here we report that a subnuclear body called the interleukin-6 and -10 splicing activating compartment (InSAC) is a nuclear site of cytokine RNA production and stability. Tat-activating regulatory DNA-binding protein-43 (TDP-43) acts as an InSAC scaffold that selectively associates with IL-6 and IL-10 RNAs in a sequence-specific manner. TDP-43 also recruits key spliceosomal components from Cajal bodies. LPS induces posttranslational modifications of TDP-43; in particular, TDP-43 ubiquitination provides a driving force for InSAC formation. As a consequence, in vivo depletion of TDP-43 leads to a dramatic reduction in the RNA processing and the protein levels of IL-6 in serum. Collectively, our findings highlight the importance of TDP-43-mediated InSAC biogenesis in immune regulation.

Suggested Citation

  • Sungwook Lee & Taeyun A. Lee & Eunhye Lee & Sujin Kang & Areum Park & Seung Won Kim & Hyo Jin Park & Je-Hyun Yoon & Sang-Jun Ha & Taesun Park & Ju-Seog Lee & Jae Hee Cheon & Boyoun Park, 2015. "Identification of a subnuclear body involved in sequence-specific cytokine RNA processing," Nature Communications, Nature, vol. 6(1), pages 1-14, May.
  • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms6791
    DOI: 10.1038/ncomms6791
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