New CRISPR approach to controlling viral infections

An international research consortium with teams from Germany, France, the United States, and Poland, and with the involvement of Sebastian Glatt, Professor of Systems Genetics at the Vetmeduni, has uncovered an entirely new CRISPR-based defense mechanism in bacteria.The findings were published in the prestigious journal Nature.

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tRNA as the virus’s Achilles’ heel

Instead of merely cleaving foreign genetic material, the newly identified CRISPR-Cas subtype Cas12a3 employs a surprising strategy: it recognizes viral RNA and, in response, triggers the precise trimming of the ends of its own tRNA molecules. This brings protein synthesis in the infected cell to a halt, stops viral replication, and thereby protects surrounding cells from further waves of infection. As a result, tRNA moves to the center of an evolutionarily conserved line of defense – an as-yet unknown dimension of the microbial immune system.

The team led by Sebastian Glatt, professor at the Center of Biological Sciences at the University of Veterinary Medicine Vienna and group leader at the Małopolska Centre of Biotechnology (MCB) of the Jagiellonian University, played a key role in the study. Andrzej Chramiec-Głąbik provided highly purified tRNA samples for structural and functional analyses, and Jakub Nowak carried out biophysical measurements of protein-RNA interactions. According to the researchers, the data show how Cas12a3 undergoes structural rearrangements to bind tRNA with exceptionally high affinity and reliably distinguish it from other RNAs. This work illustrates how a detailed understanding of naturally existing CRISPR mechanisms continue to open new perspectives for biotechnology – from designing diagnostic tools to controlling protein synthesis in specific eukaryotic cells,” says Sebastian Glatt.

The study expands the prevailing view of CRISPR systems: they can not only recognize and cleave viral genetic material but also intervene specifically in the host’s translation machinery – with tRNA as a central lever of regulation.

The project was funded by the European Research Council (ERC) under the Horizon 2020 programme (Grant No. 101001394, SG).

The article "RNA-triggered Cas12a3 cleaves tRNA tails to execute bacterial immunity” by Ole Dmytrenko et al. was published in Nature.

Scientific article

Glatt Lab

Malopolska Centre of Biotechnology

Jagiellonian University

European Research Council (ERC)

Scientific contact:
Univ.-Prof. Dr. Sebastian Glatt
Center of Biological Sciences
University of Veterinary Medicine Vienna (Vetmeduni)
Sebastian.Glatt@vetmeduni.ac.at

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