Skip to content

Research at St Andrews

Control of cyclic oligoadenylate synthesis in a type III CRISPR system

Research output: Contribution to journalArticle

DOI

Open Access permissions

Open

Author(s)

Christophe Rouillon, Januka S. Athukoralage, Shirley Graham, Sabine Grüschow, Malcolm F. White

School/Research organisations

Abstract

The CRISPR system for prokaryotic adaptive immunity provides RNA-mediated protection from viruses and mobile genetic elements. When viral RNA transcripts are detected, type III systems adopt an activated state that licenses DNA interference and synthesis of cyclic oligoadenylate (cOA). cOA activates nucleases and transcription factors that orchestrate the antiviral response. We demonstrate that cOA synthesis is subject to tight temporal control, commencing on target RNA binding, and is deactivated rapidly as target RNA is cleaved and dissociates. Mismatches in the target RNA are well tolerated and still activate the cyclase domain, except when located close to the 3' end of the target. Phosphorothioate modification reduces target RNA cleavage and stimulates cOA production. The 'RNA shredding' activity originally ascribed to type III systems may thus be a reflection of an exquisite mechanism for control of the Cas10 subunit, rather than a direct antiviral defence.
Close

Details

Original languageEnglish
Article numbere36734
Number of pages22
JournaleLife
Volume7
Early online date2 Jul 2018
DOIs
Publication statusPublished - 19 Jul 2018

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

View graph of relations

Related by author

  1. 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

  2. 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

  3. 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

  4. Ring nucleases deactivate Type III CRISPR ribonucleases by degrading cyclic oligoadenylate

    Athukoralage, J. S., Rouillon, C., Graham, S., Grüschow, S. & White, M. F., 11 Oct 2018, In : Nature. 562, 7726, p. 277-280 16 p.

    Research output: Contribution to journalArticle

  5. Phenylalanine meta-hydroxylase: a single residue mediates mechanistic control of aromatic amino acid hydroxylation

    Gruschow, S., Sadler, J., Sharrat, P. & Goss, R. J. M., 22 Nov 2019, In : ChemBioChem. Early View

    Research output: Contribution to journalArticle

Related by journal

  1. eLife (Journal)

    Will Cresswell (Reviewer)
    11 Apr 2018

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

  2. eLife (Journal)

    Christian Rutz (Member of editorial board)
    27 Jul 2016 → …

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

Related by journal

  1. ATP-induced asymmetric pre-protein folding as a driver of protein translocation through the Sec machinery

    Corey, R., Ahdash, Z., Shah, A., Pyle, E., Allen, W., Fessl, T., Lovett, J. E., Politis, A. & Collinson, I., 2 Jan 2019, In : eLife. 8, 25 p., e41803.

    Research output: Contribution to journalArticle

  2. Improved characterisation of MRSA transmission using within-host bacterial sequence diversity

    Hall, M. D., Holden, M. TG., Srisomang, P., Mahavanakul, W., Wuthiekanun, V., Limmathurotsakul, D., Fountain, K., Parkhill, J., Nickerson, E. K., Peacock, S. J. & Fraser, C., 8 Oct 2019, In : eLife. 8

    Research output: Contribution to journalArticle

  3. Large-scale replication study reveals a limit on probabilistic prediction in language comprehension

    Nieuwland, M. S., Politzer-Ahles, S., Heyselaar, E., Segaert, K., Darley, E., Kazanina, N., Von Grebmer Zu Wolfsthurn, S., Bartolozzi, F., Kogan, V., Ito, A., Mézière, D., Barr, D. J., Rousselet, G. A., Ferguson, H. J., Busch-Moreno, S., Fu, X., Tuomainen, J., Kulakova, E., Husband, E. M., Donaldson, D. I. & 4 others, Kohút, Z., Rueschemeyer, S-A., Huettig, F. & Shinn-Cunningham, B. G. (ed.), 3 Apr 2018, In : eLife. 7, 24 p., e33468.

    Research output: Contribution to journalArticle

  4. Reactive oxygen species regulate activity-dependent neuronal plasticity in Drosophila

    Oswald, M. C., Brooks, P. S., Zwart, M. F., Mukherjee, A., West, R. J., Giachello, C. N., Morarach, K., Baines, R. A., Sweeney, S. T. & Landgraf, M., 17 Dec 2018, In : eLife. 7, 27 p., e39393.

    Research output: Contribution to journalArticle

ID: 254021822

Top