1. Toxin-antitoxin RNA pairs safeguard CRISPR-Cas systems.
- Author
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Li M, Gong L, Cheng F, Yu H, Zhao D, Wang R, Wang T, Zhang S, Zhou J, Shmakov SA, Koonin EV, and Xiang H
- Subjects
- CRISPR-Associated Proteins genetics, CRISPR-Cas Systems genetics, DNA Mutational Analysis, Gene Expression Regulation, Archaeal, Haloarcula genetics, Operon, RNA, Transfer, Arg metabolism, Toxin-Antitoxin Systems genetics, CRISPR-Associated Proteins physiology, CRISPR-Cas Systems physiology, Haloarcula physiology, RNA, Archaeal physiology, Toxin-Antitoxin Systems physiology
- 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
UCU (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.)- Published
- 2021
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