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Bacterial Schlafen proteins mediate phage defence
Veronica Perez Taboada1, Yimo Wu1, Riley Cassidy1
1Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, FL, USA.
Nature Microbiology
|March 10, 2026
Summary
Prokaryotic Schlafen nucleases are ancient antiviral proteins protecting bacteria from phages by cleaving transfer RNA (tRNA). This discovery reveals the deep evolutionary origins of tRNA-targeting immunity conserved from bacteria to humans.
Area of Science:
- Microbiology
- Molecular Biology
- Immunology
Background:
- Human Schlafen proteins inhibit viral replication via tRNA cleavage, suppressing protein synthesis.
- The function of conserved Schlafen ribonuclease domains in prokaryotes remained largely unknown.
Purpose of the Study:
- To investigate the role of prokaryotic Schlafen nucleases as antiviral effectors.
- To characterize the mechanism and evolutionary origin of tRNA-targeting antiviral immunity.
Main Methods:
- Expression of seven Enterobacterales Schlafen systems in Escherichia coli.
- Functional assays to identify defense against coliphages.
- Biochemical characterization of a Schlafen-sensor domain interaction with phage components.
Main Results:
- Two Schlafen systems conferred defense against coliphages.
- A novel Schlafen-immunoglobulin-like sensor recognized T5-like phage tail assembly chaperones.
- Activated Schlafen nucleases cleaved bacterial and phage tRNA, restricting T5 phage replication by reducing burst size.
Conclusions:
- Prokaryotic Schlafen nucleases are widespread, ancient antiviral effectors in bacteria.
- The findings redefine Schlafens as mechanistically conserved immune effectors.
- This study reveals the deep evolutionary history of tRNA-targeting antiviral immunity, from prokaryotes to humans.
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