A type III CRISPR ancillary ribonuclease degrades its cyclic oligoadenylate activator
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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.
Athukoralage , J S , Graham , S , Grüschow , S , Rouillon , C & White , M F 2019 , ' A type III CRISPR ancillary ribonuclease degrades its cyclic oligoadenylate activator ' Journal of Molecular Biology , vol. 431 , no. 15 , pp. 2894-2899 . https://doi.org/10.1016/j.jmb.2019.04.041
Journal of Molecular Biology
© 2019 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
DescriptionThis work was funded by a grant from the Biotechnology and Biological Sciences Research Council (Grant REF BB/S000313/1 to MFW).
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