中文摘要：哺乳动物中，环GMP-AMP（cGAMP）合酶（cGAS）产生环二核苷酸2'3'-cGAMP以响应胞质DNA，从而触发抗病毒免疫反应。cGAS属于cGAS/DncV类核苷酸转移酶的一个大家族，存在于原核生物和真核生物中。在细菌中，这些酶合成一系列环状寡核苷酸，最近已成为噬菌体感染的重要调节因子。本研究鉴定了昆虫果蝇中的两种cGAS样受体（cGLRs），发现cGLR1和cGLR2激活Sting-和NF-κB依赖的抗病毒免疫，以应对RNA或DNA病毒感染。cGLR1被双链RNA激活以产生环状二核苷酸3'2'-cGAMP，而cGLR2产生2'3'-cGAMP和3'2'-cGAMP的组合以响应尚未识别的刺激。研究证实了cGAS是一个受体家族的创始成员，该家族通过产生2'3'-cGAMP以外的环二核苷酸来感知不同类型的核酸并触发免疫。
外文摘要：In mammals, cyclic GMP-AMP (cGAMP) synthase (cGAS) produces the cyclic dinucleotide 2'3'-cGAMP in response to cytosolic DNA and this triggers an antiviral immune response. cGAS belongs to a large family of cGAS/DncV-like nucleotidyltransferases that is present in both prokaryotes(1) and eukaryotes(2-5). In bacteria, these enzymes synthesize a range of cyclic oligonucleotides and have recently emerged as important regulators of phage infections(6-8). Here we identify two cGAS-like receptors (cGLRs) in the insect Drosophila melanogaster. We show that cGLR1 and cGLR2 activate Sting- and NF-kappa B-dependent antiviral immunity in response to infection with RNA or DNA viruses. cGLR1 is activated by double-stranded RNA to produce the cyclic dinucleotide 3'2'-cGAMP, whereas cGLR2 produces a combination of 2'3'-cGAMP and 3'2'-cGAMP in response to an as-yet-unidentified stimulus. Our data establish cGAS as the founding member of a family of receptors that sense different types of nucleic acids and trigger immunity through the production of cyclic dinucleotides beyond 2'3'-cGAMP.
外文关键词：CYCLIC GMP-AMP；CYTOSOLIC DNA SENSOR；2ND-MESSENGER；DINUCLEOTIDE；ACTIVATION; REVEALS
作者：Holleufer, A；Winther, KG；Gad, HH；Ai, XL；Chen, YQ；Li, LH；Wei, ZM；Deng, HM；Liu, JY；Frederiksen, NA；Simonsen, B；Andersen, LL；Kleigrewe, K；Dalskov, L；Pichlmair, A；Cai, H；Imler, JL；Hartmann, R
作者单位：Aarhus Univ；Univ Strasbourg；Guangzhou Med Univ；Tech Univ Munich；German Ctr Infect Res DZIF
期刊名称：NATURE
期刊影响因子：42.779
出版年份：2021
出版刊次：
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