Skip to content

Research at St Andrews

An anti-CRISPR viral ring nuclease subverts type III CRISPR immunity

Research output: Contribution to journalArticle

Author(s)

Januka Sahan Athukoralage, Stephen McMahon, Changyi Zhang, Sabine Gruschow, Shirley Graham, Mart Krupovic, Rachel Whitaker, Tracey Gloster, Malcolm White

School/Research organisations

Abstract

The CRISPR system in bacteria and archaea provides adaptive immunity against mobile genetic elements. Type III CRISPR systems detect viral RNA, resulting in the activation of two regions of the Cas10 protein: an HD nuclease domain (which degrades viral DNA)1,2 and a cyclase domain (which synthesizes cyclic oligoadenylates from ATP)3,4,5. Cyclic oligoadenylates in turn activate defence enzymes with a CRISPR-associated Rossmann fold domain6, sculpting a powerful antiviral response7,8,9,10 that can drive viruses to extinction7,8. Cyclic nucleotides are increasingly implicated in host–pathogen interactions11,12,13. Here we identify a new family of viral anti-CRISPR (Acr) enzymes that rapidly degrade cyclic tetra-adenylate (cA4). The viral ring nuclease AcrIII-1 is widely distributed in archaeal and bacterial viruses and in proviruses. The enzyme uses a previously unknown fold to bind cA4 specifically, and a conserved active site to rapidly cleave this signalling molecule, allowing viruses to neutralize the type III CRISPR defence system. The AcrIII-1 family has a broad host range, as it targets cA4 signalling molecules rather than specific CRISPR effector proteins. Our findings highlight the crucial role of cyclic nucleotide signalling in the conflict between viruses and their hosts.
Close

Details

Original languageEnglish
Pages (from-to)572-575
Number of pages19
JournalNature
Volume577
Issue number7791
Early online date15 Jan 2020
DOIs
Publication statusPublished - 23 Jan 2020

    Research areas

  • System, Evolutionary, Mechanism, Space, DNA

Discover related content
Find related publications, people, projects and more using interactive charts.

View graph of relations

Related by author

  1. Tetramerisation of the CRISPR ring nuclease Crn3/Csx3 facilitates cyclic oligoadenylate cleavage

    Athukoralage, J. S., McQuarrie, S. J., Gruschow, S., Graham, S., Gloster, T. & White, M., 28 Jun 2020, (Accepted/In press) In : eLife. In press

    Research output: Contribution to journalArticle

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

    Athukoralage, J. S., Graham, S., Rouillon, C., Gruschow, S., M Czekster, C. & White, M., 27 Apr 2020, In : eLife. 9, 16 p., e55852.

    Research output: Contribution to journalArticle

  3. Cyclic oligoadenylate signalling mediates Mycobacterium tuberculosis CRISPR defence

    Grüschow, S., Athukoralage, J. S., Graham, S., Hoogeboom, T. & White, M. F., 26 Sep 2019, In : Nucleic Acids Research. 47, 17, p. 9259-9270 12 p.

    Research output: Contribution to journalArticle

  4. A type III CRISPR ancillary ribonuclease degrades its cyclic oligoadenylate activator

    Athukoralage, J. S., Graham, S., Grüschow, S., Rouillon, C. & White, M. F., 12 Jul 2019, In : Journal of Molecular Biology. 431, 15, p. 2894-2899

    Research output: Contribution to journalArticle

  5. Investigation of the cyclic oligoadenylate signaling pathway of type III CRISPR systems

    Rouillon, C., Athukoralage, J. S., Graham, S., Grüschow, S. & White, M. F., 1 Jan 2019, Methods in Enzymology. Bailey, S. (ed.). Academic Press Inc., p. 191-218 28 p. (Methods in Enzymology; vol. 616).

    Research output: Chapter in Book/Report/Conference proceedingChapter

Related by journal

  1. Analyses of non-coding somatic drivers in 2,658 cancer whole genomes

    PCAWG Drivers and Functional Interpretation Working Group, PCAWG Structural Variation Working Group & PCAWG Consortium, 6 Feb 2020, In : Nature. 578, 7793, p. 102-111 10 p.

    Research output: Contribution to journalArticle

  2. How STRANGE are your study animals?

    Webster, M. M. & Rutz, C., 18 Jun 2020, In : Nature. 582, p. 337-340 4 p.

    Research output: Contribution to journalArticle

  3. Importance and vulnerability of the world’s water towers

    Immerzeel, W. W., Lutz, A. F., Andrade, M., Bahl, A., Biemans, H., Bolch, T., Brumby, S., Davies, B. J., Hyde, S., Elmore, A. C., Emmer, A., Feng, M., Fernández, A., Haritashya, U., Kargel, J. S., Koppes, M., Kraaijenbrink, P. D. A., Kulkarni, A. V., Mayewski, P., Nepal, S. & 12 others, Pacheco, P., Painter, T. H., Pellicciotti, F., Rajaram, H., Rupper, S., Sinisalo, A., Shrestha, A. B., Viviroli, D., Wada, Y., Xiao, C., Yao, T. & Baillie, J. E. M., 16 Jan 2020, In : Nature. 577, 7790, p. 364-369

    Research output: Contribution to journalArticle

Related by journal

  1. Nature (Journal)

    Will Cresswell (Reviewer)

    21 Dec 2017

    Activity: Publication peer-review and editorial work typesPeer review of manuscripts

  2. Nature (Journal)

    Will Cresswell (Reviewer)

    11 Nov 2017

    Activity: Publication peer-review and editorial work typesPeer review of manuscripts

  3. Nature (Journal)

    David Gerard Dritschel (Editor)

    2005 → …

    Activity: Publication peer-review and editorial work typesEditor of research journal

  4. Nature (Journal)

    Ifor David William Samuel (Editor)

    2005 → …

    Activity: Publication peer-review and editorial work typesEditor of research journal

ID: 264190868

Top