The dynamic interplay of host and viral enzymes in type III CRISPR-mediated cyclic nucleotide signalling

  1. Januka S Athukoralage
  2. Shirley Graham
  3. Christophe Rouillon
  4. Sabine Grüschow
  5. Clarissa M Czekster
  6. Malcolm F White  Is a corresponding author
  1. University of St Andrews, United Kingdom
  2. 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

  1. Januka S Athukoralage

    Biomedical Sciences Research Complex, School of Biology, University of St Andrews, St Andrews, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1666-0180
  2. Shirley Graham

    Biomedical Sciences Research Complex, School of Biology, University of St Andrews, St Andrews, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2608-3815
  3. Christophe Rouillon

    Neuroethology institute, Stiftung Caesar, Bonn, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Sabine Grüschow

    Biomedical Sciences Research Complex, School of Biology, University of St Andrews, St Andrews, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  5. Clarissa M Czekster

    School of Biology, University of St Andrews, St Andrews, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Malcolm F White

    Biomedical Sciences Research Complex, School of Biology, University of St Andrews, St Andrews, United Kingdom
    For correspondence
    mfw2@st-and.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1543-9342

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.

Reviewing Editor

  1. Blake Wiedenheft, Montana State University, United States

Publication history

  1. Received: February 12, 2020
  2. Accepted: April 26, 2020
  3. Accepted Manuscript published: April 27, 2020 (version 1)
  4. Version of Record published: May 11, 2020 (version 2)

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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  1. Januka S Athukoralage
  2. Shirley Graham
  3. Christophe Rouillon
  4. Sabine Grüschow
  5. Clarissa M Czekster
  6. Malcolm F White
(2020)
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

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