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

• Published in: eLife Vol. 9
• Main Authors: Athukoralage, Januka S, Graham, Shirley, Rouillon, Christophe, Grüschow, Sabine, Czekster, Clarissa M, White, Malcolm F
• Format: Journal Article
• Language: English
• Published: England eLife Sciences Publications Ltd 27.04.2020; eLife Sciences Publications, Ltd
• Subjects: Antiviral agents; Biochemistry and Chemical Biology; Chromatography; CRISPR; CRISPR-Cas Systems; cyclic oligoadenylate; Enzymes; Escherichia coli - enzymology; Escherichia coli - genetics; Host Microbial Interactions; Immune system; Nuclease; Nucleotides, Cyclic - metabolism; Research Advance; Ribonuclease; Ribonucleic acid; ring nuclease; RNA; Second messengers; Signal Transduction; Sulfolobus solfataricus; Sulfolobus solfataricus - genetics; Sulfolobus solfataricus - metabolism; Viruses; Viruses - enzymology; Viruses - genetics; CRISPR; chemical biology; biochemistry; Sulfolobus solfataricus; cyclic oligoadenylate; E. coli; ring nuclease; ribonuclease
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.55852

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 type III-D CRISPR complex generates cyclic tetra-adenylate (cA ), activating the ribonuclease Csx1, and showed that subsequent RNA cleavage and dissociation acts as an 'off-switch' for the cyclase activity. Subsequently, we identified the cellular ring nuclease Crn1, which slowly degrades cA to reset the system (Rouillon et al., 2018), 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.