中国科学院微生物研究所向华/李明团队合作取得最新进展。他们发现毒素-抗毒素RNA对可保护CRISPR-Cas系统。相关论文于2021年4月30日发表于国际顶尖学术期刊《科学》杂志上。

他们报告说，多亚基CRISPR效应器Cascade转录调节毒素-抗毒素RNA对-CreTA。CreT（级联抑制毒素）是一种抑菌RNA，可以隔离稀有的精氨酸tRNAUCU（通过反密码子UCU转移RNA）。CreA是一种类似于CRISPR RNA的抗毒素RNA，需要Cas6才能成熟。CreA和creT启动子之间的部分互补性指导Cascade抑制毒素转录。 因此，仅在级联的存在下，CreA才具有抗毒性。

在缺失CreTA的细胞中，级联基因变得易受转座因子破坏。他们发现了几种与不同的古细菌和细菌CRISPR-cas基因座相关的CreTA类似物。因此，毒素-抗毒素RNA对可以通过使细胞倾向于利用CRISPR-Cas来保护CRISPR免疫力，这突显了Cas蛋白的多功能性和CRISPR-Cas调控的复杂机制。

据介绍，CRISPR-Cas系统在原核生物中提供RNA指导的适应性免疫。

附：英文原文

Title: Toxin-antitoxin RNA pairs safeguard CRISPR-Cas systems

Author: Ming Li, Luyao Gong, Feiyue Cheng, Haiying Yu, Dahe Zhao, Rui Wang, Tian Wang, Shengjie Zhang, Jian Zhou, Sergey A. Shmakov, Eugene V. Koonin, Hua Xiang

Issue&Volume: 2021/04/30

Abstract: CRISPR-Cas systems provide RNA-guided adaptive immunity in prokaryotes. We report that the multisubunit CRISPR effector Cascade transcriptionally regulates a toxin-antitoxin RNA pair, CreTA. CreT (Cascade-repressed toxin) is a bacteriostatic RNA that sequesters the rare arginine tRNAUCU (transfer RNA with anticodon UCU). CreA is a CRISPR RNA–resembling antitoxin RNA, which requires Cas6 for maturation. The partial complementarity between CreA and the creT promoter directs Cascade to repress toxin transcription. Thus, CreA becomes antitoxic only in the presence of Cascade. In CreTA-deleted cells, cascade genes become susceptible to disruption by transposable elements. We uncover several CreTA analogs associated with diverse archaeal and bacterial CRISPR-cas loci. Thus, toxin-antitoxin RNA pairs can safeguard CRISPR immunity by making cells addicted to CRISPR-Cas, which highlights the multifunctionality of Cas proteins and the intricate mechanisms of CRISPR-Cas regulation.

DOI: 10.1126/science.abe5601

Source: https://science.sciencemag.org/content/372/6541/eabe5601