A cyclic oligonucleotide signaling pathway in type III CRISPR-Cas systems

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Science  29 Jun 2017:
DOI: 10.1126/science.aao0100

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Type III CRISPR-Cas systems in prokaryotes provide immunity against invading nucleic acids through the coordinated degradation of transcriptionally-active DNA and its transcripts by the Csm effector complex. Cas10 subunit of the complex contains a HD-nuclease domain responsible for DNA degradation and two Palm domains with elusive functions. In addition, Csm6, an RNase that is not part of the complex, is also required to provide full immunity. We show here that target RNA binding by the Csm effector complex of Streptococcus thermophilus triggers Cas10 to synthesize cyclic oligoadenylates cOAn (n = 2-6) via the Palm domains. Acting as signaling molecules, cOAs bind Csm6 to activate its non-specific RNA degradation. This cOA-based signaling pathway coordinates different components of CRISPR-Cas to prevent phage infection and propagation.

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