CRISPR-Cas III-A Csm6 CARF Domain Is a Ring Nuclease Triggering Stepwise cA4 Cleavage with ApA>p Formation Terminating RNase Activity (Molecular Cell)

In structure-function studies on CRISPR-Cas Csm6 RNase, Jia et al. demonstrate that its CARF domain is a ring nuclease, triggering stepwise cleavage of bound cA4 into ApApApA>p and ApA>p, using a timer mechanism to regulate HEPN domain RNase activity. We also establish that CARF domain His132 plays an autoinhibitory role in controlling RNase activity.