Protein-templated synthesis of dinucleotide repeat DNA by an antiphage reverse transcriptase
Abstract
Defense-associated reverse transcriptases (DRTs) are widespread bacterial antiphage systems that use unconventional mechanisms of polynucleotide synthesis. We show that DRT3, which comprises two distinct RTs (Drt3a and Drt3b) and a noncoding RNA (ncRNA), synthesizes alternating poly(GT/AC) double-stranded DNA. Cryo-electron microscopy structures at 2.6-angstrom resolution reveal a D3-symmetric 6:6:6 complex of Drt3a, Drt3b, and ncRNA. Drt3a produces the poly(GT) strand using a conserved ACACAC template within the ncRNA. Notably, Drt3b synthesizes a complementary, protein-primed poly(AC) strand in the complete absence of a nucleic acid template, using conserved active site residues specific to Drt3b to enforce precise base alternation. These findings expand the functional landscape of nucleic acid polymerases, revealing a protein-templated mechanism for sequence-specific DNA synthesis.
Fields of Study & Subjects
Bacterial Genetics and Biotechnology
Bacteriophages and microbial interactions
RNA and protein synthesis mechanisms
Publication details
- Journal / source
- Science
- Publisher
- American Association for the Advancement of Science (AAAS)
- Volume
- 392
- Issue
- 6804
- Pages
- 1274–1281
- Publication date
- 16 April 2026
- Language
- EN