New function of CRISPR gene scissors discovered

For several years now, the CRISPR/Cas9 gene scissors have been making waves in science and medicine.

Researchers from the Institute of Structural Biology of the University Hospital Bonn (UKB) in Germany and the Faculty of Medicine of the University of Bonn, in collaboration with the partner University of St. Andrews in Scotland and the European Laboratory of Molecular Biology in Hamburg, Germany, have discovered a new function of gene scissors. The study was published in the journal Nature.

When an attacking phage injects its genetic material into a bacterium, it is forced to produce new phages, which in turn infect more bacteria. In response, some bacteria have developed the CRISPR system. With the help of this bacterial immune system, the phage’s genetic material is recognized and destroyed.

At the same time, the obtained fragments are integrated into the genome of the bacterium. This creates a kind of library that the CRISPR immune system can access again and again and thus weaponize for future attacks. In addition, so-called type III variants of the scissor gene were found to produce small signaling molecules. With the help of these small molecules, the bacteria put together a complex emergency plan. This ensures that the virus can be fought optimally and with a broad front.

The research team discovered that the small signaling molecules bind to, among other things, a protein called CalpL, which thus becomes an active “protease.” These are enzymes that break down proteins and thus function as protein scissors.

“Proteases are also used in the human immune system to transmit information at high speed,” said Niels Schneeberger, a postdoctoral fellow at the UKB Institute of Structural Biology and one of the two first authors of the study.

Finally, the researchers also found a target for their newly discovered scissor protein. It cuts a small protein molecule called CalpT, which acts as a latch for CalpS, a third protein molecule.

“CalpS is a highly conserved protein that is secreted by the entire mechanism. This will drive the transcription machinery to specific genes, switching the bacterium’s metabolism to defense. We are very interested in finding out what these genes are,” said Christophe Rouillon, visiting scientist at the Institute of Structural Biology and first author of the study.

With the discovery of this complex signaling cascade, the researchers said they have discovered an entirely new aspect of CRISPR systems.

“With these CRISPR-activated protein scissors, there is a completely new tool in the molecular biology toolbox,” said Gregor Hageluken, group leader at UKB’s Institute of Structural Biology and member of the transdisciplinary research unit Life and Health at the University of Bonn.

“And maybe it will allow CRISPR which will be used in even more diverse ways in the future.” New function of CRISPR gene scissors discovered

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