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Updated: Sep 20, 2025
15:49
Reverse Genetics to Engineer Positive-Sense RNA Virus Variants
Published on: June 9, 2022
1.5K
Protein-primed homopolymer synthesis by an antiviral reverse transcriptase
Stephen Tang1, Rimantė Žedaveinytė1, Nathaniel Burman2
1Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA.
Nature
|May 28, 2025
Summary
Bacteria utilize defense-associated reverse transcriptase (DRT9) systems for antiviral defense. These systems synthesize DNA homopolymers, like polydeoxyadenylate, to combat phage infections and establish population-level immunity.
Area of Science:
- Microbiology
- Molecular Biology
- Bacteriology
Background:
- Bacteria possess diverse immune systems targeting foreign DNA.
- Defense-associated reverse transcriptase (DRT) systems offer an alternative defense strategy using DNA synthesis.
- DRT2 systems utilize RNA templates for de novo gene synthesis encoding antiviral proteins.
Purpose of the Study:
- To investigate if DRT9 systems employ similar defense mechanisms.
- To elucidate the function of DRT9 in bacterial antiviral defense.
- To understand the molecular mechanisms of DRT9-mediated immunity.
Main Methods:
- Cryo-electron microscopy for structural analysis.
- Biochemical and functional experiments.
- In vivo studies of DRT9 activity and regulation.
Main Results:
- DRT9 systems defend against phages via DNA homopolymer synthesis, specifically polydeoxyadenylate (poly-dA).
- Viral infection induces poly-dA accumulation, leading to abortive infection and population immunity.
- Structural and biochemical data reveal a non-coding RNA template and tyrosine residues priming DNA synthesis, forming protein-DNA adducts.
- Poly-dA synthesis is regulated by phage-encoded triggers and host-encoded silencers.
Conclusions:
- DRT9 systems represent a novel nucleic-acid-driven bacterial defense mechanism.
- This study expands the known functions of reverse transcriptases in immunity.
- Identified a unique antiviral strategy based on DNA synthesis and abortive infection.
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