NLM DIR Seminar Schedule

Abstract:

CRISPR-associated Rossmann Fold (CARF) is a key component of prokaryotic cyclic oligonucleotide-based antiphage signaling systems (CBASS) that sense cyclic oligonucleotides and transmit the signal to an effector inducing cell dormancy or death. Most of the CARFs are components of a CBASS built into type III CRISPR-Cas systems, where the CARF domain binds cyclic oligoA (cOA) synthesized by Cas10 polymerase-cyclase and allosterically activates the effector, typically, a promiscuous ribonuclease of the HEPN superfamily. Additionally, this signaling pathway includes a ring nuclease, often, also a CARF domain (either the sensor itself or a specialized enzyme) that cleaves cOA and mitigates dormancy or death induction. We present a comprehensive census of CARF domains in bacteria and archaea, and their sequence- and structure-based classification. There are 10 major families of CARF domains and multiple smaller groups that differ in structural features, association with distinct effectors, and presence or absence of the ring nuclease activity. By comparative genome analysis, we predict specific functions of CARF domains and partition the CARF domains into those with both sensor and ring nuclease functions, and sensor-only ones. Several families of ring nucleases that do not contain the CARF domain but are functionally associated with sensor-only CARF domains are also predicted.

At the end of the talk, I will give a brief update on evolution and diversity of CRISPR-Cas systems mostly focusing on the work performed in our group over the last few years.

The work is done in collaboration with Albertas Timinskas, Yuri I. Wolf, Ayal B. Gussow, Virginijus Siksnys, Leslovas Venclovas, Eugene V. Koonin