Zhang Yan, Lin Jinzhong, Feng Mingxia, She Qunxin
State Key Laboratory of Agricultural Microbiology and College of Life Science and Technology, Huazhong Agricultural University, 430070 Wuhan, China.
College of Life Science, Henan Normal University, Xinxiang, Henan 453007, China.
Emerg Top Life Sci. 2018 Dec 14;2(4):483-491. doi: 10.1042/ETLS20180023.
Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) systems provide the adaptive antiviral immunity against invasive genetic elements in archaea and bacteria. These immune systems are divided into at least six different types, among which Type III CRISPR-Cas systems show several distinct antiviral activities as demonstrated from the investigation of bacterial III-A and archaeal III-B systems in the past decade. First, although initial experiments suggested that III-A systems provided DNA interference activity, whereas III-B system was active only in RNA interference, these immune systems were subsequently found to mediate the transcription-dependent DNA interference and the dual DNA/RNA interference. Second, their ribonucleoprotein (RNP) complexes show target RNA (tgRNA) cleavage by a ruler mechanism and RNA-activated indiscriminate single-stranded DNA cleavage, the latter of which is subjected to spatiotemporal regulation such that the DNase activity occurs only at the right place in the right time. Third, RNPs of Type III systems catalyse the synthesis of cyclic oligoadenylates (cOAs) that function as second messengers to activate Csm6 and Csx1, both of which are potent Cas accessory RNases after activation. To date, Type III CRISPR systems are the only known antiviral immunity that utilizes multiple interference mechanisms for antiviral defence.
成簇规律间隔短回文重复序列（CRISPR）及其相关（Cas）系统为古细菌和细菌中的入侵遗传元件提供适应性抗病毒免疫。这些免疫系统至少分为六种不同类型，其中III型CRISPR-Cas系统表现出几种独特的抗病毒活性，这在过去十年对细菌III-A和古细菌III-B系统的研究中得到了证实。首先，尽管最初的实验表明III-A系统提供DNA干扰活性，而III-B系统仅在RNA干扰中具有活性，但随后发现这些免疫系统介导转录依赖性DNA干扰和双重DNA/RNA干扰。其次，它们的核糖核蛋白（RNP）复合物通过尺子机制显示靶RNA（tgRNA）切割和RNA激活的无差别单链DNA切割，后者受到时空调节，使得DNase活性仅在正确的时间出现在正确的位置。第三，III型系统的RNP催化环状寡腺苷酸（cOA）的合成，cOA作为第二信使激活Csm6和Csx1，这两者在激活后都是有效的Cas辅助核糖核酸酶。迄今为止，III型CRISPR系统是唯一已知的利用多种干扰机制进行抗病毒防御的抗病毒免疫。
