Toxin-antitoxin RNA pairs safeguard CRISPR-Cas systems.

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

Science (New York, N.Y.) 2021 Apr 30

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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. Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Citation

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. Toxin-antitoxin RNA pairs safeguard CRISPR-Cas systems. Science (New York, N.Y.). 2021 Apr 30;372(6541)