Discovery of a Novel CRISPR Mechanism Expands Bioeconomy Potential

CRISPR/Cas systems are considered one of the key technologies of the bioeconomy. They make it possible to precisely influence biological processes, for example for more sustainable agriculture, innovative bio-based production methods, or new diagnostic applications. New scientific findings are now expanding this potential.

A new CRISPR mechanism selectively paralyzes cells

A research team from the Helmholtz Institute for RNA-based Infection Research (HIRI) in Würzburg, together with other international research institutions, has discovered a previously unknown CRISPR defense mechanism. At its core is the nuclease Cas12a3, which differs fundamentally from known CRISPR tools because it specifically cleaves the so-called 3′ tail of transfer RNAs (tRNAs).

tRNAs are essential for protein biosynthesis because they transport amino acids to the ribosomes. If their evolutionarily highly conserved tail is removed, protein production ceases. The affected cell enters a dormant state, preventing viruses from replicating further. Thus, Cas12a3 describes a new form of bacterial immune response not previously attributed to CRISPR systems.

“This discovery was completely unexpected,” reports Chase Beisel from HIRI, corresponding author of the study. The team had originally been investigating nucleases that exclusively cut DNA. Instead, the researchers stumbled upon other members of the same protein family with entirely different properties. A scientific stroke of luck that could also enable practical applications in the future.

New perspectives for bio-based technologies

Using cryo-electron microscopy, the researchers were able to show how Cas12a3 achieves this high precision: A special “tRNA loading domain” positions the tRNA tail exactly for cutting. This accuracy makes Cas12a3 not only biologically interesting but also technologically relevant. The enzyme has already been combined with other CRISPR nucleases in the laboratory to simultaneously detect RNA from several viruses, including influenza, RSV, and SARS-CoV-2.

This discovery opens up new fields of application for the bioeconomy, particularly in molecular diagnostics. In the future, cost-effective, easy-to-use tests based on CRISPR technology could be developed. At the same time, the study underscores the vast untapped innovative potential of natural biological defense mechanisms. Researching these mechanisms can provide crucial impetus for a knowledge-based bioeconomy.

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(Featured image by MJH SHIKDER via Unsplash)

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