Cyclic oligoadenylate signaling and regulation by ring nucleases during type III CRISPR defense
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In prokaryotes, CRISPR-Cas immune systems recognise and cleave foreign nucleic acids to defend against Mobile Genetic Elements (MGEs). Type III CRISPR-Cas complexes also synthesise cyclic oligoadenylate (cOA) second messengers, which activate CRISPR ancillary proteins involved in antiviral defence. In particular, cOA-stimulated nucleases degrade RNA and DNA non-specifically, which slows MGE replication but also impedes cell growth, necessitating mechanisms to eliminate cOA in order to mitigate collateral damage. Extant cOA is degraded by a new class of enzyme termed a 'ring nuclease', which cleaves cOA specifically and switches off CRISPR ancillary enzymes. Several ring nuclease families have been characterised to date, including a family used by MGEs to circumvent CRISPR immunity, and encompass diverse protein folds and distinct cOA cleavage mechanisms. In this review we outline cOA signalling, discuss how different ring nucleases regulate the cOA signalling pathway, and reflect on parallels between cyclic nucleotide-based immune systems to reveal new areas for exploration.
Athukoralage , J S & White , M F 2021 , ' Cyclic oligoadenylate signaling and regulation by ring nucleases during type III CRISPR defense ' , RNA , vol. 27 , no. 8 , pp. 855-867 . https://doi.org/10.1261/rna.078739.121
Copyright © 2021 Athukoralage and White This article, published in RNA, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
DescriptionFunding: We thank the RNA society for an invitation to submit this work as part of a 2021 RNA Society/Sacringe Graduate Student Award. The work in the authors’ lab described in this article was supported by research grants from the Biotechnology and Biological Sciences Research Council (REF: BB/S000313/1 and BB/T004789/1).
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