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Structure paper

TitleDNA polymerization activates RNA cleavage of a reverse transcriptase-like antiviral enzyme.
Journal, issue, pagesScience, Page eaef3178, Year 2026
Publish dateMay 21, 2026
AuthorsXuejun Rong / Jun Xiao / Xinyuan Zhao / Yan Yan / Jing Li / Yifan Chen / Yihua Fan / Zhichao Liu / Yue Cao / Fan Chen / Rui Cheng / Xionglue Wang / Longfei Wang / Bin Zhu /
PubMed AbstractDefense-associated reverse transcriptases (DRTs) transcribe noncoding RNAs (ncRNAs) for antiviral defense, but the mechanisms of ncRNA-independent DRTs remain unclear. In this work, we show that a ...Defense-associated reverse transcriptases (DRTs) transcribe noncoding RNAs (ncRNAs) for antiviral defense, but the mechanisms of ncRNA-independent DRTs remain unclear. In this work, we show that a single DRT4 mediates RNA-targeting antiphage defense by integrating DNA polymerase, exonuclease, and RNA endonuclease activities. First, through an equilibrium between its DNA polymerase and exonuclease activities, DRT4 senses phage infection, as elevated dNTP levels shift the equilibrium toward polymerase activity, thereby promoting protein-primed single-stranded DNA (ssDNA) synthesis. Second, ssDNA of sufficient length, phage DNA-binding proteins, and deoxyguanosine triphosphate collectively activate an unusual RNA endonuclease activity of DRT4, excising 3'-guanosine monophosphate from both phage and host RNA to terminate infection. These findings reveal a distinctive immune strategy combining nucleic acid synthesis and degradation, expanding the functional landscape of DRTs for new DNA- and RNA-processing technologies.
External linksScience / PubMed:42166559
MethodsEM (single particle)
Resolution2.22 - 2.96 Å
Structure data

67871

21ou

EMDB-67871, PDB-21ou:
DRT4 homohexamer
Method: EM (single particle) / Resolution: 2.34 Å

67946

21ro

EMDB-67946, PDB-21ro:
DRT4 homohexamer with dGTPaS
Method: EM (single particle) / Resolution: 2.68 Å

67947

21rp

EMDB-67947, PDB-21rp:
DRT4 homohexamer with dATP
Method: EM (single particle) / Resolution: 2.84 Å

67950

21rs

EMDB-67950, PDB-21rs:
DRT4 homohexamer with dATP, dGTPaS, SSB, RNA
Method: EM (single particle) / Resolution: 2.76 Å

68056

21wo

EMDB-68056, PDB-21wo:
DRT4 homohexamer with dATP, SSB
Method: EM (single particle) / Resolution: 2.96 Å

69681

24na

EMDB-69681, PDB-24na:
DRT4 homohexamer with dGTP
Method: EM (single particle) / Resolution: 2.8 Å

69682

24nb

EMDB-69682, PDB-24nb:
DRT4 homohexamer with dGTP, GMP
Method: EM (single particle) / Resolution: 2.54 Å

69683

24nc

EMDB-69683, PDB-24nc:
DRT4 homohexamer with dGTP, RNA
Method: EM (single particle) / Resolution: 2.22 Å

69684

24nd

EMDB-69684, PDB-24nd:
DRT4 homohexamer with dGTP, ssRNA (local refinement)
Method: EM (single particle) / Resolution: 2.68 Å

Chemicals

ChemComp-T8T:
2'-deoxyguanosine-5'-O-(1-thiotriphosphate)

ChemComp-MG:
Unknown entry

ChemComp-DTP:
2'-DEOXYADENOSINE 5'-TRIPHOSPHATE

ChemComp-GMP:
GUANOSINE

ChemComp-DGT:
2'-DEOXYGUANOSINE-5'-TRIPHOSPHATE

ChemComp-DGP:
2'-DEOXYGUANOSINE-5'-MONOPHOSPHATE

Source
  • enterobacteriaceae (enterobacteria)
  • escherichia coli (E. coli)
  • dna molecule (others)
  • synthetic construct (others)
KeywordsRNA BINDING PROTEIN/DNA / DRT4; reverse transcriptase; terminal transferase; nuclease / RNA BINDING PROTEIN-DNA complex / RNA BINDING PROTEIN / IMMUNE SYSTEM

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