CRISPR-Cas Protein Roles and Teamwork

The cover of Molecular Cell in which the paper was originally published.

In this initial adaptation phase, one of two different Cas4 proteins recognizes a signaling placeholder in the sequence that occurs adjacent to the snippet of DNA that is excised.

When the Cas1 and Cas2 proteins are present in the cell with either of two Cas4 protein nucleases, Cas4-1 and Cas4-2, they act like the generals of this army-based immune system, communicating uniform sized clipped DNA fragments, directions on where to go next and ultimately instructions that destroy the lethal DNA fragment.

In order for a cell to successfully recognize and excise strands of DNA, incorporate them into its own genome and achieve immunity, the Cas4 proteins must be present in conjunction with the Cas1 and Cas2 proteins.

“Cas4 is present in many CRISPR-Cas systems, but the roles of the proteins were mysterious,” said Terns. “In our system, there are two Cas4 proteins that are essential for governing this process so that functional RNAs are made and immunity is conferred”

This is exciting new research that helps inform other researchers about the role of these particular proteins in successful immunity and contributes to larger base of knowledge with the end goal of trying to combat genetic diseases such as diabetes or cancer. Terns and Gravely have been collaborating on research for a decade now and clearly have an unwavering interest in trying to know more about this elegant RNA-based viral immune system. Great to see continued success and discovery on this topic from one of our very own. Kudos. You can read more about the study here.