Liu Chao, Wang Rui, Li Jie, Cheng Feiyue, Shu Xian, Zhao Huiwei, Xue Qiong, Yu Haiying, Wu Aici, Wang Lingyun, Hu Sushu, Zhang Yihan, Yang Jun, Xiang Hua, Li Ming
CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China; College of Life Science, University of Chinese Academy of Sciences, Beijing, China.
CAS Key Laboratory of Microbial Physiological and Metabolic Engineering, State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
Cell Host Microbe. 2023 Sep 13;31(9):1481-1493.e6. doi: 10.1016/j.chom.2023.08.005. Epub 2023 Sep 1.
CRISPR RNAs (crRNAs) and Cas proteins work together to provide prokaryotes with adaptive immunity against genetic invaders like bacteriophages and plasmids. However, the coordination of crRNA production and cas expression remains poorly understood. Here, we demonstrate that widespread modulatory mini-CRISPRs encode cas-regulating RNAs (CreRs) that mediate autorepression of type I-B, I-E, and V-A Cas proteins, based on their limited complementarity to cas promoters. This autorepression not only reduces autoimmune risks but also responds to changes in the abundance of canonical crRNAs that compete with CreR for Cas proteins. Furthermore, the CreR-guided autorepression of Cas proteins can be alleviated or even subverted by diverse bacteriophage anti-CRISPR (Acr) proteins that inhibit Cas effectors, which, in turn, promotes the generation of new Cas proteins. Our findings reveal a general RNA-guided autorepression paradigm for diverse Cas effectors, shedding light on the intricate self-coordination of CRISPR-Cas and its transcriptional counterstrategy against Acr proteins.
CRISPR RNA（crRNA）与Cas蛋白共同作用，为原核生物提供针对噬菌体和质粒等基因入侵者的适应性免疫。然而，crRNA产生与cas表达的协调机制仍知之甚少。在此，我们证明广泛存在的调控性小CRISPR编码cas调控RNA（CreR），这些RNA基于与cas启动子的有限互补性介导I-B型、I-E型和V-A型Cas蛋白的自我抑制。这种自我抑制不仅降低了自身免疫风险，还能响应与CreR竞争Cas蛋白的经典crRNA丰度变化。此外，抑制Cas效应物的多种噬菌体抗CRISPR（Acr）蛋白可减轻甚至颠覆CreR引导的Cas蛋白自我抑制，进而促进新Cas蛋白的产生。我们的发现揭示了多种Cas效应物通用的RNA引导自我抑制模式，为CRISPR-Cas复杂的自我协调及其针对Acr蛋白的转录对抗策略提供了新见解。
