The dynamic interplay of host and viral enzymes in type III CRISPR-mediated cyclic nucleotide signalling
- University of St Andrews, United Kingdom
- Stiftung Caesar, Germany
Abstract
Cyclic nucleotide second messengers are increasingly implicated in prokaryotic anti-viral defence systems. Type III CRISPR systems synthesise cyclic oligoadenylate (cOA) upon detecting foreign RNA, activating ancillary nucleases that can be toxic to cells, necessitating mechanisms to remove cOA in systems that operate via immunity rather than abortive infection. Previously, we demonstrated that the Sulfolobus solfataricus type III-D CRISPR complex generates cyclic tetra-adenylate (cA4), activating the ribonuclease Csx1, and showed that subsequent RNA cleavage and dissociation acts as an 'off-switch' for the cyclase activity (Rouillon et al., 2018). Subsequently, we identified the cellular ring nuclease Crn1, which slowly degrades cA4 to reset the system, and demonstrated that viruses can subvert type III CRISPR immunity by means of a potent anti-CRISPR ring nuclease variant AcrIII-1. Here, we present a comprehensive analysis of the dynamic interplay between these enzymes, governing cyclic nucleotide levels and infection outcomes in virus-host conflict.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been (will be) provided for Figures 2, 3, 4 and 6.
Article and author information
Author details
Januka S Athukoralage
Funding
Biotechnology and Biological Sciences Research Council (BB/S000313/1)
- Malcolm F White
Wellcome (210486/Z/18/Z)
- Clarissa M Czekster
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2020, Athukoralage et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The dynamic interplay of host and viral enzymes in type III CRISPR-mediated cyclic nucleotide signalling
eLife 9:e55852.
https://doi.org/10.7554/eLife.55852
