Bacteria defend against invading viruses with molecular scissors that slice the viral DNA. A system called CRISPR has become essential for gene editing.
But the virus can fight back with molecular tricks that stop the scissors from being produced. Writing in progress natureScientists at the University of California, San Francisco describe how the viral “anti-CRISPR” protein sits on the bacterial protein assembly line known as the ribosome and blocks it as the CRISPR protein, named Cas12, begins to form. This activates the quality control mechanisms of the ribosome and destroys the emerging protein and its mRNA blueprint.
A viral protein called AcrVA2 is the only anti-CRISPR known to interfere with CRISPR in this way.
When AcrVA2 was first introduced into bacterial cells together with Cas12, we observed that Cas12 disappeared. We thought that anti-CRISPR only captured Cas proteins to prevent cleavage, but this was fundamentally different. ”
Dr. Joseph Bondi Denomy, Research Senior Author and Professor of Microbiology and Immunology, University of California, San Francisco
Ribosomes produce Cas12 based on genetic instructions stored in the bacterial DNA. These instructions are copied into a molecular blueprint called mRNA. The ribosome then uses the mRNA to assemble Cas12 one amino acid at a time.
Scientists led by Dr. Nicole Marino tested each step from DNA to mRNA to protein to pinpoint when Cas12 is lost. AcrVA2 did not block the Cas12 gene, which should prevent Cas12 mRNA production, nor did it destroy mRNA in vitro. So scientists investigated whether anti-CRISPR was doing anything to ribosomes.
They discovered that AcrVA2 stands by while ribosomes make one protein after another. But as soon as AcrVA2 saw the first few amino acids of Cas12 begin to appear, it grabbed the growing protein and brought the assembly line to a halt.
“This anti-CRISPR holds the ribosome in one hand and selects just one protein, Cas12, in the other hand,” Bondi Denomy said. “The ribosome is forced to treat a healthy message like a defective message.”
When the ribosome becomes clogged, the bacterial quality control machinery destroys both the budding Cas12 protein and its mRNA blueprint.
This discovery appears to be the first of its kind to show that one protein interferes with the production of another protein on the ribosome. This is just the latest twist in our understanding of the evolutionary competition between bacteria and viruses.
sauce:
University of California, San Francisco
Reference magazines:
Marino, North Dakota; others (2026). Translation-dependent degradation of cas12 mRNA induced by anti-CRISPR. nature. DOI: 10.1038/s41586-026-10440-8. https://www.nature.com/articles/s41586-026-10440-8.
