华中科技大学朱斌团队与武汉大学王隆飞团队合作发现DNA聚合激活逆转录样抗病毒酶的RNA裂解。这一研究成果于2026年5月21日发表在国际顶尖学术期刊《科学》上。

在这项工作中，课题组研究人员表明单个DRT4通过整合DNA聚合酶、核酸外切酶和RNA内切酶活性来介导RNA靶向噬菌体防御。首先，通过DNA聚合酶和外切酶活性之间的平衡，DRT4感知噬菌体感染，因为升高的dNTP水平将平衡转向聚合酶活性，从而促进蛋白引物单链DNA （ssDNA）的合成。其次，足够长度的ssDNA、噬菌体DNA结合蛋白和脱氧鸟苷三磷酸共同激活DRT4的非胞内切酶活性，从噬菌体和宿主RNA中切除3′-鸟苷一磷酸，以终止感染。这些发现揭示了一种结合核酸合成和降解的独特免疫策略，为新的DNA和RNA加工技术扩展了DRT的功能景观。

据介绍，防御相关逆转录酶（DRTs）转录非编码RNA（ncRNA）用于抗病毒防御，但不依赖ncRNA的DRTs的机制尚不清楚。

附：英文原文

Title: DNA polymerization activates RNA cleavage of a reverse transcriptase–like antiviral enzyme

Author: 荣雪君)

Issue&Volume: 2026-05-21

Abstract: 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: aef3178

Source: https://www.science.org/doi/10.1126/science.aef3178

期刊信息

Science：《科学》，创刊于1880年。隶属于美国科学促进会，最新IF：63.714

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