Scientists at the Life Sciences Center of Vilnius University (VU LSC) have published a new study in the prestigious journal Nature Structural & Molecular Biology. The publication reveals a previously poorly understood antiviral defence mechanism in bacteria, whose underlying principles could be applied to the development of new genome-editing or biological control tools.

Researchers Monika Jasnauskaitė (PhD student), Jonas Juozapaitis (PhD student), Toma Liegutė (PhD student), Dr Rokas Grigaitis, Dr Aistė Skorupskaitė, Dr Wieland Steinchen, Algirdas Mikšys (PhD student), Dr Lidija Truncaitė, Kristina Kazlauskaitė (PhD student), Dr María F. Torres Jimenez, Sharvika Subodh Khochare (PhD student), Dr Gytis Dudas, Prof Gert Bange, Dr Lina Malinauskaitė, Dr Inga Songailienė, and Dr Patrick Pausch investigated a specialised bacterial system known as the Eco2 retron. This system comprises a unique protein-DNA complex that senses viral enzymes and initiates a protective response.

A Self-Defence Strategy That Disrupts Protein Synthesis in Bacteria

Bacteria are constantly attacked by viruses known as bacteriophages. To survive, they have evolved various defence systems. One of these is the Eco2 retron, an antiviral system composed of a single protein and a single-stranded DNA molecule it produces, called msDNA.

According to M. Jasnauskaitė, a PhD researcher working in Dr P. Pausch’s laboratory, the Eco2 protein contains two functional domains: one enzyme that synthesises DNA from RNA, and another that cleaves RNA molecules.

“Under normal conditions, the system remains inactive. The msDNA molecule acts like a safety lock – it physically blocks the RNA-cutting part of the protein, preventing it from cleaving RNAs,” she explains.

“At first, it was unclear what exactly activates this mechanism. Our results showed that Eco2 is activated when a virus begins to degrade the DNA molecule it produces. In other words, the viral attack itself becomes the signal for the bacterium to enter defence mode,” says M. Jasnauskaitė.

When infecting a bacterial cell, the virus introduces its own DNA-degrading enzyme, called DenB. This enzyme begins to break down msDNA, which in turn triggers the protective mechanism.

“Once msDNA is degraded, the RNA-cutting part of the protein becomes active and begins cleaving transfer RNA molecules required for protein synthesis. Without them, the virus can no longer produce its components and replicate,” explains Dr P. Pausch.

A Unique Protein Structure Enables Defence

To understand how this mechanism works at the molecular level, the researchers used cryo-electron microscopy, a method that allows scientists to visualise protein structures at near-atomic resolution.

“We discovered that Eco2 forms a complex composed of three identical subunits arranged symmetrically around a central axis. The msDNA molecule plays a dual role: it not only connects the protein components but also physically blocks the RNA-cutting site. As long as this DNA remains intact, the system stays switched off,” says M. Jasnauskaitė.

When the viral enzyme degrades msDNA, the protein structure undergoes subtle changes that allow RNA cleavage to begin. The study showed that once activated, Eco2 primarily targets specific transfer RNA (tRNA) molecules, thereby halting protein production.

According to M. Jasnauskaitė, this discovery demonstrates that even minimal molecular systems can function as precisely regulated biological switches. A detailed structural understanding of this system also opens the door to future biotechnological applications.

Broad Implications for Biotechnology

“Experiments showed that the Eco2 system provides broad antiviral protection against bacteriophages from different families. This suggests that such minimal systems are efficient immune systems against viruses, and explains why they are so widespread in nature,” says Dr P. Pausch.

Beyond its fundamental biological significance, the discovery also holds applied potential. Because retrons produce DNA molecules and respond to specific molecular signals, their principles could be applied to develop new genome-editing or biological-control tools.

This study represents another important contribution by VU researchers to the global understanding of antiviral defence systems. It expands our knowledge of how even simple molecular components can be harnessed to solve complex biological challenges.