本研究表明，DRT9与其上游非编码RNA （ncRNA）形成六聚体复合物，通过流产感染诱导细胞生长停滞，介导抗噬菌体防御。在噬菌体感染后，噬菌体编码的核糖核苷酸还原酶NrdAB复合物增加细胞内脱氧腺苷三磷酸水平，激活DRT9合成长且富含聚腺苷酸[poly(A)]的单链互补DNA (cDNA)，这可能会隔离必需的噬菌体单链DNA结合（SSB）蛋白并破坏噬菌体的繁殖。该团队进一步确定了DRT9-ncRNA六聚体复合体的低温电镜结构，为其cDNA合成提供了机制见解。这些发现突出了基于RT的抗病毒防御机制的多样性，扩展了他们对RT生物学功能的理解，并为开发基于DRT9的生物技术工具提供了结构基础。
据悉，原核防御相关逆转录酶（DRTs）最近被发现具有抗病毒功能；然而，它们的功能机制在很大程度上仍未被探索。
附：英文原文
Title: Bacterial reverse transcriptase synthesizes long poly(A)-rich cDNA for antiphage defense
Author: Xin-Yi Song, Yushan Xia, Jun-Tao Zhang, Yu-Jun Liu, Hua Qi, Xin-Yang Wei, Hailiang Hu, Yu Xia, Xue Liu, Ying-Fei Ma, Ning Jia
Issue&Volume: 2025-06-19
Abstract: Prokaryotic defense-associated reverse transcriptases (DRTs) were recently identified with antiviral functions; however, their functional mechanisms remain largely unexplored. Here we show that DRT9 forms a hexameric complex with its upstream noncoding RNA (ncRNA) to mediate antiphage defense by inducing cell growth arrest through abortive infection. Upon phage infection, the phage-encoded ribonucleotide reductase NrdAB complex increases intracellular deoxyadenosine triphosphate levels, activating DRT9 to synthesize long, polyadenylate [poly(A)]–rich single-stranded complementary DNA (cDNA), which likely sequesters the essential phage single-stranded DNA binding (SSB) protein and disrupts phage propagation. We further determined the cryo–electron microscopy structure of the DRT9-ncRNA hexamer complex, providing mechanistic insights into its cDNA synthesis. These findings highlight the diversity of RT-based antiviral defense mechanisms, expand our understanding of RT biological functions, and provide a structural basis for developing DRT9-based biotechnological tools.
DOI: ads4639
Source: https://www.science.org/doi/10.1126/science.ads4639