The targeted degradation of foreign nucleic acids by type III CRISPR–Cas systems is mediated by the multisubunit Csm interference complex. In addition, the CRISPR-associated protein Csm6 ribonuclease, which does not form part of the Csm complex, degrades foreign RNAs to provide full immunity, but how these two processes are linked is unknown. Now, two new studies reveal the mechanistic link between invader sensing and the activity of Csm6. Both studies by Kazlauskiene et al. and Niewoehner, Garcia-Doval et al. discovered that RNA binding by the Csm complex triggers its Cas10 subunit to synthesize cyclic oligoadenylate from ATP, which then binds to Csm6 and allosterically activates its ribonuclease activity. Together, these studies reveal a signalling pathway in bacteria that is reminiscent of signalling in mammalian innate immunity to control viral infection.
References
Kazlauskiene, M. et al. A cyclic oligonucleotide signaling pathway in type III CRISPR–Cas systems. Science http://dx.doi.org/10.1126/science.aao0100 (2017)
Niewoehner, O., Garcia-Doval, C. et al. Type III CRISPR–Cas systems produce cyclic oligoadenylate second messengers. Nature http://dx.doi.org/10.1038/nature23467 (2017)
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York, A. Raising the alarm. Nat Rev Microbiol 15, 513 (2017). https://doi.org/10.1038/nrmicro.2017.92
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DOI: https://doi.org/10.1038/nrmicro.2017.92