Prokaryotes are equipped with a variety of resistance strategies to survive frequent viral attacks or invading mobile genetic elements. Among these, CRISPR–Cas surveillance systems are abundant and have been studied extensively. This Review focuses on CRISPR–Cas type VI Cas13 systems that use single-subunit RNA-guided Cas endonucleases for targeting and subsequent degradation of foreign RNA, thereby providing adaptive immunity. Notably, distinct from single-subunit DNA-cleaving Cas9 and Cas12 systems, Cas13 exhibits target RNA-activated substrate RNase activity. This Review outlines structural, biochemical and cell biological studies toward elucidation of the unique structural and mechanistic principles underlying surveillance effector complex formation, precursor CRISPR RNA (pre-crRNA) processing, self-discrimination and RNA degradation in Cas13 systems as well as insights into suppression by bacteriophage-encoded anti-CRISPR proteins and regulation by endogenous accessory proteins. Owing to its programmable ability for RNA recognition and cleavage, Cas13 provides powerful RNA targeting, editing, detection and imaging platforms with emerging biotechnological and therapeutic applications.

原核生物配备了多种抵抗策略，可以在频繁的病毒攻击或入侵的移动遗传元件中生存。其中，CRISPR-Cas监控系统非常丰富，并已被广泛研究。本综述重点关注 CRISPR–Cas VI 型 Cas13 系统，该系统使用单亚基 RNA 引导的 Cas 核酸内切酶来靶向并随后降解外源 RNA，从而提供适应性免疫。值得注意的是，与单亚基 DNA 切割 Cas9 和 Cas12 系统不同，Cas13 表现出目标 RNA 激活底物 RNase 活性。本综述概述了结构、生化和细胞生物学研究，旨在阐明 Cas13 系统中监视效应复合物形成、前体 CRISPR RNA (pre-crRNA) 处理、自我歧视和 RNA 降解的独特结构和机制原理，以及对抑制的见解通过噬菌体编码的抗 CRISPR 蛋白和内源辅助蛋白的调节。由于其 RNA 识别和切割的可编程能力，Cas13 为新兴的生物技术和治疗应用提供了强大的 RNA 靶向、编辑、检测和成像平台。