Decreased Dicer expression elicits DNA damage and up-regulation of MICA and MICB
Open Access
- 21 July 2008
- journal article
- Published by Rockefeller University Press in The Journal of cell biology
- Vol. 182 (2), 233-239
- https://doi.org/10.1083/jcb.200801169
Abstract
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.Keywords
This publication has 30 references indexed in Scilit:
- Transcription and RNAi in heterochromatic gene silencingNature Structural & Molecular Biology, 2007
- mRNA degradation by miRNAs and GW182 requires both CCR4:NOT deadenylase and DCP1:DCP2 decapping complexesGenes & Development, 2006
- Is RNA interference involved in intrinsic antiviral immunity in mammals?Nature Immunology, 2006
- The Human LINE-1 Retrotransposon Creates DNA Double-strand BreaksJournal of Molecular Biology, 2006
- Shaping time: chromatin structure and the DNA replication programmeTrends in Genetics, 2005
- Histone H2A phosphorylation in DNA double‐strand break repairThe FEBS Journal, 2005
- Nucleic acid structure and intracellular immunity: some recent ideas from the world of RNAiQuarterly Reviews of Biophysics, 2005
- Ago1 and Dcr1, Two Core Components of the RNA Interference Pathway, Functionally Diverge from Rdp1 in Regulating Cell Cycle Events inSchizosaccharomyces pombeMolecular Biology of the Cell, 2004
- Short-Interfering-RNA-Mediated Gene Silencing in Mammalian Cells Requires Dicer and eIF2C Translation Initiation FactorsCurrent Biology, 2003
- ATF3 induction following DNA damage is regulated by distinct signaling pathways and over-expression of ATF3 protein suppresses cells growthOncogene, 2002