Toxin-antitoxin RNA pairs safeguard CRISPR-Cas systems.

Li, Ming; Gong, Luyao; Cheng, Feiyue; Yu, Haiying; Zhao, Dahe; Wang, Rui; Wang, Tian; Zhang, Shengjie et al. · Science · 2021

basic_science · Level V

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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 tRNA<sup>UCU</sup> (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 <i>creT</i> promoter directs Cascade to repress toxin transcription. Thus, CreA becomes antitoxic only in the presence of Cascade. In CreTA-deleted cells, <i>cascade</i> genes become susceptible to disruption by transposable elements. We uncover several CreTA analogs associated with diverse archaeal and bacterial CRISPR-<i>cas</i> 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.

Medical subject headings