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| Title | DNA polymerization activates RNA cleavage of a reverse transcriptase-like antiviral enzyme. |
|---|---|
| Journal, issue, pages | Science, Page eaef3178, Year 2026 |
| Publish date | May 21, 2026 |
 Authors | Xuejun 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 Abstract | 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 ...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 links | Science / PubMed:42166559 |
| Methods | EM (single particle) |
| Resolution | 2.22 - 2.96 Å |
| Structure data | EMDB-67871, PDB-21ou: EMDB-67946, PDB-21ro: EMDB-67947, PDB-21rp: EMDB-67950, PDB-21rs: EMDB-68056, PDB-21wo: EMDB-69681, PDB-24na: EMDB-69682, PDB-24nb: EMDB-69683, PDB-24nc: EMDB-69684, PDB-24nd: |
| Chemicals |  ChemComp-T8T:  ChemComp-MG:  ChemComp-DTP:  ChemComp-GMP:  ChemComp-DGT:  ChemComp-DGP: |
| Source |
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 Keywords | RNA BINDING PROTEIN/DNA / DRT4; reverse transcriptase; terminal transferase; nuclease / RNA BINDING PROTEIN-DNA complex / RNA BINDING PROTEIN / IMMUNE SYSTEM |
enterobacteriaceae (enterobacteria)
escherichia coli (E. coli)
