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• W2951567133 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." @default.
• W2951567133 created "2019-06-27" @default.
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• W2951567133 date "2019-07-01" @default.
• W2951567133 modified "2023-10-12" @default.
• W2951567133 title "A Type III CRISPR Ancillary Ribonuclease Degrades Its Cyclic Oligoadenylate Activator" @default.
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• W2951567133 doi "https://doi.org/10.1016/j.jmb.2019.04.041" @default.
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