DNA scissors can cut RNA as well

Our ability to change the content of genes at will is undergoing a revolution, driven by the discovery of CRISPR-Cas9 — a technology based on the immune system of bacteria, which cuts DNA out of invading viruses.

Now, German scientists have discovered that CRISPR-Cas9 can also readily target RNA, in a breakthrough that could have far-reaching ramifications.

By recognising and cutting foreign genomic material (DNA) from invading viruses, the CRISPR-Cas9 immune system protects bacteria from being infected. The cutting is performed by the Cas9 protein, which acts as a pair of scissors, while other parts of the system act as guides that instruct where Cas9 should cut the DNA.

Scientists have been harnessing these molecular scissors for a few years now in combination with artificial guides to specifically modify genes — not only in bacteria but also in plants and animals. But while these scissors are known to typically cut DNA, researchers from the Julius-Maximilians-Universität Würzburg (JMU) and the Helmholtz Institute for RNA-based Infection Research (HIRI) have now shown that the abilities of the Cas9 protein of the foodborne pathogen Campylobacter jejuni are not solely limited to DNA.

“Instead, the protein is also capable of cutting related molecules, called ribonucleic acids — RNA for short,” said Professor Cynthia Sharma from the JMU. “Not only that, but we found that we could also program this Cas9 to target and cut specific RNA molecules.”

A major role of RNAs is to serve as messenger of genomic material in the cell: genes, stored in the DNA, are extracted by transcribing them into RNA. The RNA then serves as a template for the translation of this information into proteins.

The researchers made their discovery while looking at molecules that interact with the Cas9 in Campylobacter. These included numerous RNAs from the cell. Further analyses showed that Cas9 not only bound but could also cut the RNA in a similar way as it does with DNA — and that it could be easily instructed to cut specific RNAs.

“The finding was surprising, given that Cas9 is thought to naturally target DNA only,” said Professor Chase Beisel, who recently joined HIRI from NC State University and has been collaborating with Professor Sharma on the project.

Published in the journal Molecular Cell, the study raises the question of whether the ability of Cas9 to target RNA has any physiological roles in Campylobacter. For instance, evidence is accumulating that CRISPR-Cas systems might not only serve to combat infections, but might rather be naturally involved in controlling which genes in Campylobacter are turned on and off.

Furthermore, the findings come soon after two other groups of researchers recently reported similar findings with Cas9s from two other bacteria. This raises the possibility that this new discovery could be a general trait of Cas9 proteins in nature.

One thing is certain: the ability to target RNA instead of DNA expands how Cas9 scissors can be used. Potential uses range from controlling which genes are turned off or on to combatting human viruses that are made of RNA to rapidly detecting infectious agents.

“We continue to be amazed by what Cas9 is capable of doing and what new applications and technologies these insights create,” said Professors Sharma and Beisel.

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