Dual phage sensing activates an RNA-targeting reverse transcriptase for anti-phage defense

DRT4 is a dual-sensor antiphage reverse transcriptase that integrates two phage-derived signals to activate dNTP-dependent RNase activity via DRT4-generated ssDNA.

• Why it matters: How defense-associated reverse transcriptases sense phage infection and couple unconventional DNA synthesis to antiviral effector activation is not well understood.
• What they did: Cryo-EM shows DRT4 forms a dimer-of-trimers hexamer, where each protomer performs protein-primed, template-independent ssDNA synthesis; phage escape genetics identify NrdAB and SSB-like protein 0087 as activators.
• The result: Activated DRT4 links phage sensing to RNA cleavage through dNTP-dependent RNase activity, implying DRT4-generated ssDNA serves as a signaling intermediate for antiviral effector activation.