Z-nucleic-acid sensing triggers ZBP1-dependent necroptosis and inflammation

doi:10.1038/s41586-020-2129-8

GSTDTAP > 地球科学

DOI	10.1038/s41586-020-2129-8
	Z-nucleic-acid sensing triggers ZBP1-dependent necroptosis and inflammation
	Zhang, Zhibin 1,2; Zhang, Ying 1,2; Xia, Shiyu 1,3; Kong, Qing 4,5; Li, Shunying 6; Liu, Xing 1,2,7; Junqueira, Caroline 1,2,8; Meza-Sosa, Karla F.1,2,9; Mok, Temy Mo Yin 1,2,10; Ansara, James 1,2; Sengupta, Satyaki 2,11; Yao, Yandan 6; Wu, Hao 1,3; Lieberman, Judy 1,2
	2020-03-01
发表期刊	NATURE
ISSN	0028-0836
EISSN	1476-4687
出版年	2020
卷号	580 期号:7803 页码:391-+
文章类型	Article
语种	英语
国家	Germany; USA; England
英文关键词	The biological function of Z-DNA and Z-RNA, nucleic acid structures with a left-handed double helix, is poorly understood(1-3). Z-DNA-binding protein 1 (ZBP1 also known as DAI or DLM-1) is a nucleic acid sensor that contains two Z alpha domains that bind Z-DNA(4,5) and Z-RNA(6-8). ZBP1 mediates host defence against some viruses(6,7,9-14) by sensing viral nucleic acids(6,7,10). RIPK1 deficiency, or mutation of its RIP homotypic interaction motif (RHIM), triggers ZBP1-dependent necroptosis and inflammation in mice(15,16). However, the mechanisms that induce ZBP1 activation in the absence of viral infection remain unknown. Here we show that Z alpha-dependent sensing of endogenous ligands induces ZBP1-mediated perinatal lethality in mice expressing RIPK1 with mutated RHIM (Ripk1(mR/mR)), skin inflammation in mice with epidermis-specific RIPK1 deficiency (RIPK1(E-KO)) and colitis in mice with intestinal epithelial-specific FADD deficiency (FADD(IEC-KO)). Consistently, functional Z alpha domains were required for ZBP1-induced necroptosis in fibroblasts that were treated with caspase inhibitors or express RIPK1 with mutated RHIM. Inhibition of nuclear export triggered the Z alpha-dependent activation of RIPK3 in the nucleus resulting in cell death, which suggests that ZBP1 may recognize nuclear Z-form nucleic acids. We found that ZBP1 constitutively bound cellular double-stranded RNA in a Z alpha-dependent manner. Complementary reads derived from endogenous retroelements were detected in epidermal RNA, which suggests that double-stranded RNA derived from these retroelements may act as a Z alpha-domain ligand that triggers the activation of ZBP1. Collectively, our results provide evidence that the sensing of endogenous Z-form nucleic acids by ZBP1 triggers RIPK3-dependent necroptosis and inflammation, which could underlie the development of chronic inflammatory conditions-particularly in individuals with mutations in RIPK1 and CASP8(17-20).
领域	地球科学 ; 气候变化 ; 资源环境
收录类别	SCI-E
WOS记录号	WOS:000530151300033
WOS关键词	Z-DNA ; BINDING DOMAIN ; RNA ; PROTEIN ; INHIBITION ; NECROSIS ; REVEALS ; COMPLEX ; RIP3
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/281249
专题	地球科学资源环境科学气候变化
作者单位	1.Boston Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA; 2.Harvard Med Sch, Dept Pediat, Boston, MA 02115 USA; 3.Harvard Med Sch, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA; 4.Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA; 5.Harvard Med Sch, Dept Genet, Boston, MA 02115 USA; 6.Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Breast Tumor Ctr, Guangzhou, Peoples R China; 7.Chinese Acad Sci, Inst Pasteur Shanghai, Ctr Microbes Dev & Hlth, Key Lab Mol Virol & Immunol, Shanghai, Peoples R China; 8.Fundacao Oswaldo Cruz, Rene Rachou Inst, Belo Horizonte, MG, Brazil; 9.Univ Nacl Autonoma Mexico, Inst Biotecnol, Lab Neuroimmunobiol, Dept Med Mol & Bioproc, Cuernavaca, Morelos, Mexico; 10.City Univ Hong Kong, Dept Biomed Sci, Hong Kong, Peoples R China; 11.Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA
推荐引用方式 GB/T 7714	Zhang, Zhibin,Zhang, Ying,Xia, Shiyu,et al. Z-nucleic-acid sensing triggers ZBP1-dependent necroptosis and inflammation[J]. NATURE,2020,580(7803):391-+.
APA	Zhang, Zhibin.,Zhang, Ying.,Xia, Shiyu.,Kong, Qing.,Li, Shunying.,...&Lieberman, Judy.(2020).Z-nucleic-acid sensing triggers ZBP1-dependent necroptosis and inflammation.NATURE,580(7803),391-+.
MLA	Zhang, Zhibin,et al."Z-nucleic-acid sensing triggers ZBP1-dependent necroptosis and inflammation".NATURE 580.7803(2020):391-+.