分解激活Retron-Septu以进行抗噬菌体防御。
Disassembly activates Retron-Septu for antiphage defense.
作者信息
Wang Chen, Rish Anthony D, Armbruster Emily G, Xie Jiale, Loveland Anna B, Shen Zhangfei, Gu Bradley, Korostelev Andrei A, Pogliano Joe, Fu Tian-Min
机构信息
Department of Pathology, UMass Chan Medical School, Worcester, MA, USA.
RNA Therapeutics Institute, UMass Chan Medical School, Worcester, MA, USA.
出版信息
Science. 2025 Jun 12:eadv3344. doi: 10.1126/science.adv3344.
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.
反转录子是一种产生多拷贝单链DNA（msDNA）的抗噬菌体防御系统，有望用于基因组工程。然而，其防御机制仍不清楚。Retron-Septu系统独特地整合了反转录子和Septu抗噬菌体防御。冷冻电子显微镜结构揭示了不对称核蛋白复合物，其由逆转录酶（RT）、msDNA（msdDNA和msrRNA的杂交体）以及两个PtuAB拷贝组成。msdDNA和msrRNA对于组装该复合物至关重要，msrRNA采用保守的套索状结构来调节逆转录。值得注意的是，组装好的Retron-Septu复合物是无活性的，msdDNA占据了PtuA DNA结合位点。在复合物解体时发生激活，释放出PtuAB，PtuAB降解单链DNA以限制噬菌体复制。这种“捕获-释放”机制突出了msDNA的动态调节作用，增进了我们对抗噬菌体防御策略的理解。
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