Toxin-antitoxin RNA pairs safeguard CRISPR-Cas systems

被引：69

作者：

Li, Ming ^{[1
,2
,3
]}

Gong, Luyao ^{[1
,3
]}

Cheng, Feiyue ^{[1
,3
]}

Yu, Haiying ^{[1
]}

Zhao, Dahe ^{[1
]}

Wang, Rui ^{[1
,3
,7
]}

Wang, Tian ^{[4
]}

Zhang, Shengjie ^{[1
,3
]}

Zhou, Jian ^{[1
]}

Shmakov, Sergey A. ^{[5
]}

Koonin, Eugene, V ^{[5
]}

Xiang, Hua ^{[1
,3
,6
]}

机构：

[1] Chinese Acad Sci, Inst Microbiol, State Key Lab Microbial Resources, Beijing, Peoples R China

[2] Chinese Acad Sci, CAS Key Lab Microbial Physiol & Metab Engn, Beijing, Peoples R China

[3] Univ Chinese Acad Sci, Coll Life Sci, Beijing, Peoples R China

[4] Sichuan Normal Univ, Coll Life Sci, Chengdu, Peoples R China

[5] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA

[6] Chinese Acad Sci, Ctr Ocean Megasci, Qingdao, Peoples R China

[7] Chengdu Med Coll, Noncoding RNA & Drug Discovery Key Lab Sichuan Pr, Chengdu, Sichuan, Peoples R China

来源：

SCIENCE | 2021年 / 372卷 / 6541期

基金：

国家重点研发计划; 美国国家卫生研究院; 中国国家自然科学基金;

关键词：

EVOLUTIONARY CLASSIFICATION; GENE-EXPRESSION; IN-VIVO; SEQUENCE; INTERFERENCE; TERMINATION; ADAPTATION; ARCHAEA; CODONS; BURST;

D O I：

10.1126/science.abe5601

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：481 / +

页数：39

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