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

被引：65

作者：

Tang, Kai-Fu ^{[1
]}

Ren, Hong ^{[1
]}

Cao, Jia ^{[2
]}

Zeng, Gui-Li ^{[1
]}

Xie, Jing ^{[1
]}

Chen, Min ^{[1
]}

Wang, Lu ^{[2
]}

He, Cai-Xia ^{[1
]}

机构：

[1] Chongqing Med Univ, Affiliated Hosp 2, Key Lab Mol Biol Infect Dis, State Minist Educ,Inst Viral Hepatitis, Chongqing 400010, Peoples R China

[2] Third Mil Med Univ, Prevent Med Coll, Hyg Toxicol Dept, Chongqing 400038, Peoples R China

来源：

JOURNAL OF CELL BIOLOGY | 2008年 / 182卷 / 02期

关键词：

D O I：

10.1083/jcb.200801169

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：233 / 239

页数：7

共 30 条

[1] MRNA degradation by miRNAs and GW182 requires both CCR4:NOT deadenylase and DCP1:DCP2 decapping complexes [J].