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

Authors
 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 
Citation
 Nature Communications, Vol.6 : 5791, 2015 
Journal Title
 Nature Communications 
ISSN
 2041-1723 
Issue Date
2015
MeSH
Animals ; DNA-Binding Proteins/metabolism* ; Electrophoretic Mobility Shift Assay ; Enzyme-Linked Immunosorbent Assay ; Humans ; Immunity, Cellular/genetics* ; Immunoblotting ; Immunoprecipitation ; In Situ Hybridization, Fluorescence ; Interleukin-10/metabolism ; Interleukin-6/metabolism ; Intranuclear Space/physiology* ; Lipopolysaccharides ; Mice ; Mice, Inbred C57BL ; RNA Interference ; RNA Processing, Post-Transcriptional/physiology* ; Real-Time Polymerase Chain Reaction ; Spliceosomes/metabolism* ; Ubiquitination
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.
Full Text
http://www.nature.com/ncomms/2015/150105/ncomms6791/full/ncomms6791.html
DOI
10.1038/ncomms6791
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Seung Won(김승원) ORCID logo https://orcid.org/0000-0002-1692-1192
Cheon, Jae Hee(천재희) ORCID logo https://orcid.org/0000-0002-2282-8904
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/139238
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