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Decreased Dicer expression elicits DNA damage and up-regulation of MICA and MICB

RNA interference (RNAi) acts constitutively to silence the innate immune response, and innate immunity genes are misregulated in Dicer-deficient Caenorhabditis elegans. Here, we show that inhibition of Dicer expression by RNAi in human cells up-regulates major histocompatibility complex class I–rela...

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Autores principales: Tang, Kai-Fu, Ren, Hong, Cao, Jia, Zeng, Gui-Li, Xie, Jing, Chen, Min, Wang, Lu, He, Cai-Xia
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2483517/
https://www.ncbi.nlm.nih.gov/pubmed/18644891
http://dx.doi.org/10.1083/jcb.200801169
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author Tang, Kai-Fu
Ren, Hong
Cao, Jia
Zeng, Gui-Li
Xie, Jing
Chen, Min
Wang, Lu
He, Cai-Xia
author_facet Tang, Kai-Fu
Ren, Hong
Cao, Jia
Zeng, Gui-Li
Xie, Jing
Chen, Min
Wang, Lu
He, Cai-Xia
author_sort Tang, Kai-Fu
collection PubMed
description RNA interference (RNAi) acts constitutively to silence the innate immune response, and innate immunity genes are misregulated in Dicer-deficient Caenorhabditis elegans. Here, we show that inhibition of Dicer expression by RNAi in human cells up-regulates major histocompatibility complex class I–related molecules A and B (MICA and MICB). MICA and MICB are innate immune system ligands for the NKG2D receptor expressed by natural killer cells and activated CD8(+)T cells. We reveal that knockdown of Dicer elicits DNA damage. Up-regulation of MICA and MICB by Dicer knockdown is prevented by pharmacologic or genetic inhibition of DNA damage pathway components, including ataxia telangiectasia mutated (ATM) kinase, ATM- and Rad3-related kinase, or checkpoint kinase 1. Therefore we conclude that up-regulation of MICA and MICB is the result of DNA damage response activation caused by Dicer knockdown. Our results suggest that RNAi is indirectly linked to the human innate immune system via the DNA damage pathway.
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spelling pubmed-24835172009-01-28 Decreased Dicer expression elicits DNA damage and up-regulation of MICA and MICB Tang, Kai-Fu Ren, Hong Cao, Jia Zeng, Gui-Li Xie, Jing Chen, Min Wang, Lu He, Cai-Xia J Cell Biol Research Articles RNA interference (RNAi) acts constitutively to silence the innate immune response, and innate immunity genes are misregulated in Dicer-deficient Caenorhabditis elegans. Here, we show that inhibition of Dicer expression by RNAi in human cells up-regulates major histocompatibility complex class I–related molecules A and B (MICA and MICB). MICA and MICB are innate immune system ligands for the NKG2D receptor expressed by natural killer cells and activated CD8(+)T cells. We reveal that knockdown of Dicer elicits DNA damage. Up-regulation of MICA and MICB by Dicer knockdown is prevented by pharmacologic or genetic inhibition of DNA damage pathway components, including ataxia telangiectasia mutated (ATM) kinase, ATM- and Rad3-related kinase, or checkpoint kinase 1. Therefore we conclude that up-regulation of MICA and MICB is the result of DNA damage response activation caused by Dicer knockdown. Our results suggest that RNAi is indirectly linked to the human innate immune system via the DNA damage pathway. The Rockefeller University Press 2008-07-28 /pmc/articles/PMC2483517/ /pubmed/18644891 http://dx.doi.org/10.1083/jcb.200801169 Text en © 2008 Tang et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Tang, Kai-Fu
Ren, Hong
Cao, Jia
Zeng, Gui-Li
Xie, Jing
Chen, Min
Wang, Lu
He, Cai-Xia
Decreased Dicer expression elicits DNA damage and up-regulation of MICA and MICB
title Decreased Dicer expression elicits DNA damage and up-regulation of MICA and MICB
title_full Decreased Dicer expression elicits DNA damage and up-regulation of MICA and MICB
title_fullStr Decreased Dicer expression elicits DNA damage and up-regulation of MICA and MICB
title_full_unstemmed Decreased Dicer expression elicits DNA damage and up-regulation of MICA and MICB
title_short Decreased Dicer expression elicits DNA damage and up-regulation of MICA and MICB
title_sort decreased dicer expression elicits dna damage and up-regulation of mica and micb
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2483517/
https://www.ncbi.nlm.nih.gov/pubmed/18644891
http://dx.doi.org/10.1083/jcb.200801169
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