逆转录酶是一种产生多拷贝单链DNA （msDNA）的噬菌体防御系统，有望用于基因组工程。
然而，其防御机制尚不清楚。逆转录-Septu系统独特地集成了逆转录和Septu抗噬菌体防御。低温电镜结构显示不对称核蛋白复合物包括逆转录酶（RT）、msDNA （msdDNA和msrRNA的杂交）和两个PtuAB拷贝。msdDNA和msrRNA对于组装该复合体至关重要，其中msrRNA采用保守的lariat样结构来调节逆转录。值得注意的是，组装的Retron-Septu复合体是无活性的，msdDNA占据了PtuA DNA结合位点。激活发生在分解时，释放PtuAB，其降解单链DNA以限制噬菌体复制。这种“捕获-释放”机制强调了msDNA的动态调控作用，促进了他们对抗噬菌体防御策略的理解。
附：英文原文
Title: Disassembly activates Retron-Septu for antiphage defense
Author: 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
Issue&Volume: 2025-06-12
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.
DOI: adv3344
Source: https://www.science.org/doi/10.1126/science.adv3344