title: Identification of a subnuclear body involved in sequence-specific cytokine RNA processing.
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.
authors.affiliation: Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749, South Korea.
authors.forename: Sungwook
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749, South Korea.
authors.forename: Taeyun A
authors.initials: TA
authors.lastname: Lee
authors.affiliation: Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749, South Korea.
authors.forename: Eunhye
authors.initials: E
authors.lastname: Lee
authors.affiliation: Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749, South Korea.
authors.forename: Sujin
authors.initials: S
authors.lastname: Kang
authors.affiliation: Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749, South Korea.
authors.forename: Areum
authors.initials: A
authors.lastname: Park
authors.affiliation: 1] Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 120-752, South Korea [2] Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul 120-752, South Korea.
authors.forename: Seung Won
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, South Korea.
authors.forename: Hyo Jin
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Laboratory of Genetics, National Institute on Aging-Intramural Research Program, NIH, Baltimore, Maryland 21224, USA.
authors.forename: Je-Hyun
authors.initials: JH
authors.lastname: Yoon
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, South Korea.
authors.forename: Sang-Jun
authors.initials: SJ
authors.lastname: Ha
authors.affiliation: Department of Food and Nutrition, College of Human Ecology, Yonsei University, Seoul 120-749, South Korea.
authors.forename: Taesun
authors.initials: T
authors.lastname: Park
authors.affiliation: Department of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, Texas 77054, USA.
authors.forename: Ju-Seog
authors.initials: JS
authors.lastname: Lee
authors.affiliation: 1] Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul 120-752, South Korea [2] Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul 120-752, South Korea.
authors.forename: Jae Hee
authors.initials: JH
authors.lastname: Cheon
authors.affiliation: Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-749, South Korea.
authors.forename: Boyoun
authors.initials: B
authors.lastname: Park
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007111:Immunity, Cellular / Q000235:genetics*; D015151:Immunoblotting; D047468:Immunoprecipitation; D017404:In Situ Hybridization, Fluorescence; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D042581:Intranuclear Space / Q000502:physiology*; D008070:Lipopolysaccharides; D051379:Mice; D008810:Mice, Inbred C57BL; D034622:RNA Interference; D012323:RNA Processing, Post-Transcriptional / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D017381:Spliceosomes / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D004268:DNA-Binding Proteins; D016753:Interleukin-10; D015850:Interleukin-6; D008070:Lipopolysaccharides; C578077:Tardbp protein, mouse