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

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

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish
Article number5791
JournalNature communications
Volume6
DOIs
Publication statusPublished - 2015 Jan 5

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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