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

Bacterial defense amplification Prokaryotic type III CRISPR systems use the effector complex and additional proteins such as Csm6 to destroy both the genome and the transcripts of invaders. However, how the effector complex and Csm6 coordinate CRISPR activity remains a mystery. Kazlauskiene et al. found that a cyclic oligonucleotide–based signaling pathway can regulate the defense response (see the Perspective by Amitai and Sorek). Upon target recognition, the Cas10 subunit of the effector complex synthesizes cyclic oligoadenylates, which act as second messengers to initiate and amplify the nuclease activity of Csm6. Science , this issue p. 605 ; see also p. 550