Disassembly activates Retron-Septu for antiphage defense.

Authors

Chen Wang, Anthony D Rish, Emily G Armbruster, Jiale Xie, Anna B Loveland, Zhangfei Shen, Bradley Gu, Andrei A Korostelev, Joe Pogliano, Tian-Min Fu

Published in

Science (New York, N.Y.). Pages eadv3344. Jun 12, 2025. Epub Jun 12, 2025.

Abstract

Retrons are antiphage defense systems that produce multicopy single-stranded DNA (msDNA) and hold promises for genome engineering. However, the mechanisms of defense remain unclear. The Retron-Septu system uniquely integrates retron and Septu antiphage defenses. Cryo-electron microscopy structures reveal asymmetric nucleoprotein complexes comprising a reverse transcriptase (RT), msDNA (a hybrid of msdDNA and msrRNA), and two PtuAB copies. msdDNA and msrRNA are essential for assembling this complex, with msrRNA adopting a conserved lariat-like structure that regulates reverse transcription. Notably, the assembled Retron-Septu complex is inactive, with msdDNA occupying the PtuA DNA-binding site. Activation occurs upon disassembly, releasing PtuAB, which degrades single-stranded DNA to restrict phage replication. This "arrest-and-release" mechanism underscores the dynamic regulatory roles of msDNA, advancing our understanding of antiphage defense strategies.

PMID:
40504952
Bibliographic data and abstract were imported from PubMed on 13 Jun 2025.

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