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KMID : 0624620150480050239
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BMB Reports
2015 Volume.48 No. 5 p.239 ~ p.240
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InSAC: A novel sub-nuclear body essential for Interleukin-6 and -10 RNA processing and stability
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Lee Sung-Wook
Park Bo-Youn
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Abstract
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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 lipopolysaccharide (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.
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KEYWORD
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TDP-43, Cytokine, IL-6, Nuclear body, RNA processing
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