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A type III CRISPR ancillary ribonuclease degrades its cyclic oligoadenylate activator

Research output: Contribution to journalArticlepeer-review

Author(s)

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

School/Research organisations

Abstract

Cyclic oligoadenylate (cOA) secondary messengers are generated by type III CRISPR systems in response to viral infection. cOA allosterically activates the CRISPR ancillary ribonucleases Csx1/Csm6, which degrade RNA non-specifically using a HEPN (Higher Eukaryotes and Prokaryotes, Nucleotide binding) active site. This provides effective immunity but can also lead to growth arrest in infected cells, necessitating a means to deactivate the ribonuclease once viral infection has been cleared. In the crenarchaea, dedicated ring nucleases degrade cA4 (cOA consisting of 4 AMP units), but the equivalent enzyme has not been identified in bacteria. We demonstrate that, in Thermus thermophilus HB8, the uncharacterized protein TTHB144 is a cA4-activated HEPN ribonuclease that also degrades its activator. TTHB144 binds and degrades cA4 at an N-terminal CARF (CRISPR-associated Rossman fold) domain. The two activities can be separated by site-directed mutagenesis. TTHB144 is thus the first example of a self-limiting CRISPR ribonuclease.
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Details

Original languageEnglish
Pages (from-to)2894-2899
JournalJournal of Molecular Biology
Volume431
Issue number15
Early online date6 May 2019
DOIs
Publication statusPublished - 12 Jul 2019

    Research areas

  • CRISPR, Anti-viral signaling, Cyclic oligoadenylate, Ring nuclease, Thermus thermophilus

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