中文摘要：环嘧啶3',5'-环胞苷单磷酸（cCMP）和3',5'-环尿苷单磷酸（cUMP）已在多种生物体和细胞类型中被报道。与环核苷酸3',5'-环腺苷单磷酸（cAMP）和3',5'-环鸟苷单磷酸（cGMP）相反，它们是第二信使分子，在生命的所有领域都具有公认的调节作用，但环嘧啶的生物学作用仍不清楚。本文报道了cCMP和cUMP是在针对病毒的细菌免疫中发挥作用的第二信使。研究发现了一个细菌嘧啶环化酶家族，在噬菌体感染后专门合成cCMP和cUMP，并证明这些分子激活免疫效应，执行抗病毒反应。来自该家族的尿苷酸环化酶的晶体结构解释了嘧啶作为环化底物选择性的分子机制。编码嘧啶环化酶的防御系统，Pycsar(嘧啶环化酶抗噬菌体抗性系统)，在原核生物中广泛存在。本研究结果明确了cCMP和cUMP作为细菌免疫信号分子的生物学功能。
外文摘要：The cyclic pyrimidines 3',5'-cyclic cytidine monophosphate (cCMP) and 3',5'-cyclic uridine monophosphate (cUMP) have been reported in multiple organisms and cell types. As opposed to the cyclic nucleotides 3',5' cyclic adenosine monophosphate (cAMP) and 3',5'-cyclic guanosine monophosphate (cGMP), which are second messenger molecules with well-established regulatory roles across all domains of life, the biological role of cyclic pyrimidines has remained unclear. Here we report that cCMP and cUMP are second messengers functioning in bacterial immunity against viruses. We discovered a family of bacterial pyrimidine cyclase enzymes that specifically synthesize cCMP and cUMP following phage infection and demonstrate that these molecules activate immune effectors that execute an antiviral response. A crystal structure of a uridylate cyclase enzyme from this family explains the molecular mechanism of selectivity for pyrimidines as cyclization substrates. Defense systems encoding pyrimidine cyclases, denoted here Pycsar (pyrimidine cyclase system for antiphage resistance), are widespread in prokaryotes. Our results assign clear biological function to cCMP and cUMP as immunity signaling molecules in bacteria.
外文关键词：MULTIPLE SEQUENCE ALIGNMENT；ADENYLYL CYCLASES；GUANYLYL CYCLASE；CCMP；IDENTIFICATION；CUMP；GMP；MODEL；CGMP
作者：Tal, N；Morehouse, BR；Millman, A；Stokar-Avihail, A；Avraham, C；Fedorenko, T；Yirmiya, E；Herbst, E；Brandis, A；Mehlman, T；Oppenheimer-Shaanan, Y；Keszei, AFA；Shao, SC；Amitai, G；Kranzusch, PJ；Sorek, R
作者单位：Weizmann Inst Sci；Harvard Med Sch；Dana Farber Canc Inst
期刊名称：CELL
期刊影响因子：38.637
出版年份：2021
出版刊次：23
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