The Hebrew University and University of Illinois teams discovered a small phage RNA, PreS, that functions as a molecular switch to reprogram bacterial gene expression and boost viral replication. PreS unfolds a section of the mRNA encoding DnaN, increasing that protein's production and accelerating phage DNA replication; removing PreS weakens the phage. The conserved nature of PreS suggests RNA regulators may be widespread in phages and could guide development of more precise phage therapies.
Tiny Viral RNA 'Switch' Discovered — A New Angle Against Antibiotic Resistance
A microscope. (photo credit: Itzik Bellenitzki/TPS)
Researchers from the Hebrew University of Jerusalem and the University of Illinois Urbana-Champaign have identified a tiny phage RNA that acts as a molecular "switch" to reprogram bacterial gene expression — a mechanism that could inform next-generation phage therapies for drug‑resistant infections.
Key discovery: The team, led by Dr. Sahar Melamed with collaborators including Aviezer Silverman, Raneem Nashef, Reut Wasserman and Prof. Ido Golding, studied a short bacteriophage RNA called PreS. Unlike most prior work that focused on phage proteins, this study shows that the well-studied lambda phage uses an RNA molecule to directly manipulate bacterial gene expression.
How PreS works
PreS binds to a folded region of specific bacterial messenger RNAs and remodels their structure. A principal target is the transcript encoding DnaN, a protein required for DNA replication. By unfolding that mRNA segment, PreS makes it more accessible to the bacterial translation machinery, increasing DnaN production. Higher DnaN levels accelerate viral DNA replication and make the phage infection more efficient.
Functional evidence
When PreS is deleted or its binding site is disrupted in laboratory experiments, the phage replicates more slowly and the lytic (destructive) phase of infection is delayed, demonstrating that this RNA is important for infection efficiency.
All yogurt contains live bacteria as part of the fermentation process (credit: SHUTTERSTOCK)
Broader significance
Small RNAs were not previously considered central to phage biology, but PreS is highly conserved across related phages, suggesting an underappreciated network of RNA-based regulators. Understanding these mechanisms can inform both basic biology and applied efforts to engineer phages for therapeutic or biotechnological purposes.
Potential applications and caveats
Insights from PreS could help design smarter, more predictable phage therapies targeting multi‑drug‑resistant bacteria and could enable synthetic‑biology applications such as biofilm control or microbiome management. However, translating such findings into clinical treatments will require extensive safety testing and consideration of ecological impacts.
Publication
The study appears in the peer‑reviewed journal Molecular Cell.
