Widespread RNA-based cas regulation monitors crRNA abundance and anti-CRISPR proteins

CRISPR RNAs (crRNAs) and Cas proteins work together to provide prokaryotes with adaptive immunity against genetic invaders like bacteriophages and plasmids. However, the coordination of crRNA production and cas expression remains poorly understood. Here, we demonstrate that widespread modulatory min...

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Bibliographic Details
Published in:	Cell host & microbe Vol. 31; no. 9; pp. 1481 - 1493.e6
Main Authors:	Liu, Chao, Wang, Rui, Li, Jie, Cheng, Feiyue, Shu, Xian, Zhao, Huiwei, Xue, Qiong, Yu, Haiying, Wu, Aici, Wang, Lingyun, Hu, Sushu, Zhang, Yihan, Yang, Jun, Xiang, Hua, Li, Ming
Format:	Journal Article
Language:	English
Published:	Elsevier Inc 13-09-2023
Subjects:	anti-CRISPR autoimmunity autoregulation Cas12a CRISPR-Cas CRISPR-Cas anti-CRISPR autoregulation Cas12a autoimmunity
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Summary:	CRISPR RNAs (crRNAs) and Cas proteins work together to provide prokaryotes with adaptive immunity against genetic invaders like bacteriophages and plasmids. However, the coordination of crRNA production and cas expression remains poorly understood. Here, we demonstrate that widespread modulatory mini-CRISPRs encode cas-regulating RNAs (CreRs) that mediate autorepression of type I-B, I-E, and V-A Cas proteins, based on their limited complementarity to cas promoters. This autorepression not only reduces autoimmune risks but also responds to changes in the abundance of canonical crRNAs that compete with CreR for Cas proteins. Furthermore, the CreR-guided autorepression of Cas proteins can be alleviated or even subverted by diverse bacteriophage anti-CRISPR (Acr) proteins that inhibit Cas effectors, which, in turn, promotes the generation of new Cas proteins. Our findings reveal a general RNA-guided autorepression paradigm for diverse Cas effectors, shedding light on the intricate self-coordination of CRISPR-Cas and its transcriptional counterstrategy against Acr proteins. [Display omitted] •Identification of a class of cas-regulating RNA (CreR) species that resemble crRNAs•CreR mediates autorepression of type I and V-A Cas effectors to reduce autoimmune risks•CreR monitors the level of typical crRNAs to proportionately fine-tune cas expression•CreR oversees the inhibition of Cas effectors by phage anti-CRISPR proteins Liu et al. report a class of crRNA-resembling RNAs that direct the autoregulation of type I and V-A Cas effectors. These cas-regulating RNA (CreR) molecules not only reduce the risk of CRISPR-Cas autoimmunity but also monitor the cellular level of typical crRNAs and surveil Cas inhibition by bacteriophage anti-CRISPR proteins.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1931-3128 1934-6069 1934-6069
DOI:	10.1016/j.chom.2023.08.005