Laboratory of Microbiology, Wageningen University and Research, Wageningen, The Netherlands.
Biochem Soc Trans. 2022 Oct 31;50(5):1353-1364. doi: 10.1042/BST20220289.
Type III CRISPR-Cas systems make use of a multi-subunit effector complex to target foreign (m)RNA transcripts complementary to the guide/CRISPR RNA (crRNA). Base-pairing of the target RNA with specialized regions in the crRNA not only triggers target RNA cleavage, but also activates the characteristic Cas10 subunit and sets in motion a variety of catalytic activities that starts with the production of cyclic oligoadenylate (cOA) second messenger molecules. These messenger molecules can activate an extensive arsenal of ancillary effector proteins carrying the appropriate sensory domain. Notably, the CARF and SAVED effector proteins have been responsible for renewed interest in type III CRISPR-Cas due to the extraordinary diversity of defenses against invading genetic elements. Whereas only a handful of CARF and SAVED proteins have been studied so far, many of them seem to provoke abortive infection, aimed to kill the host and provide population-wide immunity. A defining feature of these effector proteins is the variety of in silico-predicted catalytic domains they are fused to. In this mini-review, we discuss all currently characterized type III-associated CARF and SAVED effector proteins, highlight a few examples of predicted CARF and SAVED proteins with interesting predicted catalytic activities, and speculate how they could contribute to type III immunity.
III 型 CRISPR-Cas 系统利用多亚基效应复合物靶向与指导/CRISPR RNA（crRNA）互补的外来（m）RNA 转录本。靶 RNA 与 crRNA 中特定区域的碱基配对不仅触发靶 RNA 切割，还激活特征性 Cas10 亚基，并引发一系列催化活性，首先产生环状寡腺苷酸（cOA）第二信使分子。这些信使分子可以激活带有适当感应结构域的大量辅助效应蛋白。值得注意的是，由于针对入侵遗传元件的防御具有非凡的多样性，CARF 和 SAVED 效应蛋白引起了人们对 III 型 CRISPR-Cas 的重新关注。尽管迄今为止仅研究了少数 CARF 和 SAVED 蛋白，但其中许多似乎引发了无效感染，旨在杀死宿主并提供全人群免疫。这些效应蛋白的一个定义特征是它们融合到的各种计算机预测的催化结构域。在这篇迷你综述中，我们讨论了所有目前表征的 III 型相关 CARF 和 SAVED 效应蛋白，强调了一些具有有趣预测催化活性的预测 CARF 和 SAVED 蛋白的例子，并推测它们如何有助于 III 型免疫。
