DNA polymerization activates RNA cleavage of a reverse transcriptase-like antiviral enzyme
Summary
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
Content
# DNA polymerization activates RNA cleavage of a reverse transcriptase-like antiviral enzyme
*Published: 2026 May 21*
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.
DOI: 10.1126/science.aef3178