Protein-primed DNA homopolymer synthesis by an antiviral reverse transcriptase

Area of Science:

• Microbiology
• Molecular Biology
• Immunology

Background:

• Bacteria possess diverse immune systems targeting foreign DNA.
• Defense-associated reverse transcriptase (DRT) systems offer an alternative defense strategy using DNA synthesis.
• Previous research focused on DRT2 systems, leaving other DRT families unexplored.

Purpose of the Study:

• To investigate the defense mechanisms of DRT9 systems.
• To uncover novel pathways of bacterial antiviral defense.

Main Methods:

• Cryo-electron microscopy (Cryo-EM) for structural analysis.
• Biochemical and functional experiments.
• In vivo studies of poly-dA synthesis regulation.

Main Results:

• DRT9 systems synthesize polydeoxyadenylate (poly-dA) upon viral infection, inducing abortive infection and population immunity.
• A conserved noncoding RNA acts as a scaffold and template for poly-dA synthesis.
• Conserved tyrosine residues in the reverse transcriptase prime DNA synthesis, forming protein-DNA adducts.
• Phage and host factors regulate DRT9-mediated poly-dA synthesis.

Conclusions:

• DRT9 represents a novel nucleic acid-driven bacterial defense mechanism.
• This system expands the understanding of bacterial immunity and reverse transcriptase functions.