Bacterial Schlafens mediate anti-phage defense

Area of Science:

• Molecular Biology
• Immunology
• Microbiology

Background:

• Human Schlafen proteins are known to restrict viral replication by cleaving transfer RNA (tRNA), inhibiting protein synthesis.
• The ribonuclease domain of Schlafen proteins is conserved across all domains of life, but its function in prokaryotes was previously unknown.

Purpose of the Study:

• To investigate the function of prokaryotic Schlafen nucleases (pSlfns) as antiviral effectors in bacteria.
• To characterize the mechanism of action for a specific pSlfns system fused to an immunoglobulin-like sensor domain.

Main Methods:

• Investigated the role of pSlfns in bacterial defense against phage infection.
• Focused on a pSlfns system fused to an immunoglobulin-like sensor domain.
• Identified phage tail assembly chaperones as targets recognized by the sensor domain.

Main Results:

• Prokaryotic Schlafen nucleases (pSlfns) are widespread and function as antiviral effectors in bacteria.
• The studied pSlfns system recognizes T5-like phage tail assembly chaperones.
• pSlfns cleave both bacterial and viral tRNA, leading to abortive infection.

Conclusions:

• Schlafen nucleases represent an ancient and conserved family of immune effectors across life.
• The findings reveal the deep evolutionary origins of tRNA-targeting antiviral immunity, linking prokaryotic and human systems.
• This study redefines the role of Schlafens as crucial components of innate immunity in bacteria and humans.