Antiviral reverse transcriptase-primase synthesizes protein-templated DNA

Authors

Song, X.-Y., Xia, Y., Zhang, J.-T., Wei, X.-Y., Qi, H., Li, L., Jia, N.

Abstract

Defense-associated reverse transcriptases (DRTs) are widespread in bacteria, but how multi-domain DRTs containing RT and additional catalytic activities coordinate antiviral defense remains unclear. Here we show that DRT7, which contains both reverse transcriptase (RT) and primase-polymerase (PP) domains, provides broad-spectrum anti-phage immunity through abortive infection and can be activated by a phage-encoded putative transcriptional regulator. Upon activation, DRT7 synthesizes long, protein-primed, palindromic poly(A)/poly(T)-rich duplex-like DNA. Cryo-electron microscopy structures reveal that RT initiates protein-primed, protein-templated, sequence-specific poly(T) synthesis through an arginine-rich recognition pocket without requiring a complementary nucleic acid template, thereby converting DRT7 from an inactive closed dimer to an active open dimer. The RT-produced poly(T) then serves as both primer and template for PP-mediated poly(A) extension, with iterative handoff between RT and PP generating palindromic, alternating poly(A)/poly(T) ssDNA tracts that assemble into fold-back duplex-like DNA. These findings uncover an unexpected antiviral strategy based on protein self-templating, sequence-specific duplex-like DNA synthesis and reveal how coupling RTs with additional catalytic activities expands the functional scope of nucleic acid synthesis pathways.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 20 Apr 2026.

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