Researchers at Rockefeller’s Laboratory of Bacteriology and the MSKCC’s Structural Biology Laboratory have discovered a new way CRISPR systems fight viruses. The system, called CRISPR-Cas10, uses genetic scissors to snip out problematic DNA, but also produces toxic molecules that flood cells and prevent virus spread.
The discovery provides a new type of immune strategy for CRISPR systems, which are already known to have multiple ways to defend against pathogens. The researchers found that the CRISPR-Cas10 system produces small molecules called cyclic-oligoadenylates (cOAs) that help shut down cell activity, preventing viruses from spreading.
The two-part response is largely a matter of timing, says co-first author Christian Baca. One part uses genetic scissors to snip out problematic DNA early in the viral infection, while the other part kicks in later using cOAs to prevent virus spread. This response is similar to how mammalian innate immunity pathways work.
The researchers used advanced molecular and structural analysis techniques to understand how this new CRISPR system works. They found that a protein called Cad1 is responsible for producing ITP, which turns toxic to cells at high levels, shutting down cell activity.
While the exact mechanism behind ITP production is unclear, the discovery has potential applications as a diagnostic tool for infections. The presence of ITP would indicate that a pathogen transcript is present in a sample, allowing for early detection and treatment.
Source: https://www.rockefeller.edu/news/36859-a-new-chemistry-for-crispr/