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InSAC: A novel sub-nuclear body essential for Interleukin-6 and -10 RNA processing and stability
InSAC: A novel sub-nuclear body essential for Interleukin-6 and -10 RNA processing and stability
BMB Reports. 2015. May, 48(5): 239-240
Copyright © 2015, Korean Society for Biochemistry and Molecular Biology
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
  • Received : March 31, 2015
  • Published : May 31, 2015
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About the Authors
Sungwook Lee
Boyoun Park
bypark@yonsei.ac.kr

Abstract
Dysregulation of cytokine expression causes inflammatory diseases or chronic infection conditions. We have identified that Tat-activating regulatory DNA-binding protein-43 (TDP-43) is involved in cytokine RNA processing in order to promote an optimal immune response. The interaction of TDP-43 with spliceosomal components from the Cajal body leads to the formation of a novel sub-nuclear body called the Interleukin (IL)-6 and IL-10 Splicing Activating Compartment (InSAC). TDP-43 binds to the IL-6 and IL-10 RNAs in a sequence-dependent manner. In cell-based studies, we observed that lipopoly-saccharide (LPS) stimulation induces the formation of the InSAC through TDP-43 ubiquitination, thereby influencing the processing and expression levels of IL-6 RNA. Moreover, TDP-43 knockdown in vivo results in a decrease in IL-6 production and its RNA splicing and stability. Thus, these findings demonstrate that the InSAC is linked to the activation and modulation of the immune response. [BMB Reports 2015; 48(5): 239-240]
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Acknowledgements
This study was supported by grants from the National Research Foundation of Korea (NRF) (2011-0015372) and from the National R&D Program, Ministry of Health & Welfare, Republic of Korea (1220060, HI14C2542).
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