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Z-nucleic-acid sensing triggers ZBP1-dependent necroptosis and inflammation 期刊论文
NATURE, 2020, 580 (7803) : 391-+
作者:  Zhang, Zhibin;  Zhang, Ying;  Xia, Shiyu;  Kong, Qing;  Li, Shunying;  Liu, Xing;  Junqueira, Caroline;  Meza-Sosa, Karla F.;  Mok, Temy Mo Yin;  Ansara, James;  Sengupta, Satyaki;  Yao, Yandan;  Wu, Hao;  Lieberman, Judy
收藏  |  浏览/下载：11/0  |  提交时间：2020/07/03

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).


  
Curtailment of renewable energy in Northwest China and market-based solutions 期刊论文
ENERGY POLICY, 2018, 123: 494-502
作者:  Liu, Shiyu;  Bie, Zhaohong;  Lin, Jiang;  Wang, Xifan
收藏  |  浏览/下载：0/0  |  提交时间：2019/04/09
Renewable energy curtailment  Trans-regional barriers  Market-based mechanisms  Spot market  Ancillary service market  
Evidence for Majorana bound states in an iron-based superconductor 期刊论文
SCIENCE, 2018, 362 (6412) : 333-335
作者:  Wang, Dongfei;  Kong, Lingyuan;  Fan, Peng;  Chen, Hui;  Zhu, Shiyu;  Liu, Wenyao;  Cao, Lu;  Sun, Yujie;  Du, Shixuan;  Schneeloch, John;  Zhong, Ruidan;  Gu, Genda;  Fu, Liang;  Ding, Hong;  Gao, Hong-Jun
收藏  |  浏览/下载：7/0  |  提交时间：2019/11/27