Control of cyclic oligoadenylate synthesis in a type III CRISPR system

112Citations
Citations of this article
101Readers
Mendeley users who have this article in their library.

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.

Cite

CITATION STYLE

APA

Rouillon, C., Athukoralage, J. S., Graham, S., Grüschow, S., & White, M. F. (2018). Control of cyclic oligoadenylate synthesis in a type III CRISPR system. ELife, 7. https://doi.org/10.7554/eLife.36734

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free