PT  - JOURNAL ARTICLE
AU  - Omar O. Abudayyeh
AU  - Jonathan S. Gootenberg
AU  - Silvana Konermann
AU  - Julia Joung
AU  - Ian M. Slaymaker
AU  - David B.T. Cox
AU  - Sergey Shmakov
AU  - Kira S. Makarova
AU  - Ekaterina Semenova
AU  - Leonid Minakhin
AU  - Konstantin Severinov
AU  - Aviv Regev
AU  - Eric S. Lander
AU  - Eugene V. Koonin
AU  - Feng Zhang
TI  - C2c2 is a single-component programmable RNA-guided RNA-targeting CRISPR effector
AID  - 10.1101/054742
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 054742
4099  - http://biorxiv.org/content/early/2016/05/21/054742.short
4100  - http://biorxiv.org/content/early/2016/05/21/054742.full
AB  - The CRISPR-Cas adaptive immune system defends microbes against foreign genetic elements via DNA or RNA-DNA interference. We characterize the Class 2 type VI-A CRISPR-Caseffector C2c2 and demonstrate its RNA-guided RNase function. C2c2 from the bacterium Leptotrichia shahii provides interference against RNA phage.In vitro biochemical analysis show that C2c2 is guided by a single crRNA and can be programmed to cleave ssRNA targets carrying complementary protospacers. In bacteria, C2c2 can be programmed to knock down specific mRNAs. Cleavage is mediated by catalytic residues in the two conserved HEPN domains, mutations in which generate catalytically inactive RNA-binding proteins. These results broaden our understanding of CRISPR-Cas systems and suggest that C2c2 can be used to develop new RNA-targeting tools.