TY - JOUR TI - The dynamic interplay of host and viral enzymes in type III CRISPR-mediated cyclic nucleotide signalling AU - Athukoralage, Januka S AU - Graham, Shirley AU - Rouillon, Christophe AU - Grüschow, Sabine AU - Czekster, Clarissa M AU - White, Malcolm F A2 - Wiedenheft, Blake A2 - Storz, Gisela A2 - Lawrence, Martin A2 - Sorek, Rotem VL - 9 PY - 2020 DA - 2020/04/27 SP - e55852 C1 - eLife 2020;9:e55852 DO - 10.7554/eLife.55852 UR - https://doi.org/10.7554/eLife.55852 AB - 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. Subsequently, we identified the cellular ring nuclease Crn1, which slowly degrades cA4 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. KW - CRISPR KW - Sulfolobus solfataricus KW - cyclic oligoadenylate KW - ribonuclease KW - ring nuclease JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -