Bacterial reverse transcriptase synthesizes long poly(A)-rich cDNA for antiphage defense

• 成果类型: Article
• 署名作者: Song, Xin-Yi; Xia, Yushan; Zhang, Jun-Tao; Liu, Yu-Jun; Qi, Hua; Wei, Xin-Yang; Hu, Hailiang; Xia, Yu; Liu, Xue; Ma, Ying-Fei; Jia, Ning
• 署名单位: Southern University of Science & Technology; Southern University of Science & Technology; Shenzhen University; Chinese Academy of Sciences; Shenzhen Institute of Advanced Technology, CAS; Southern University of Science & Technology; Southern University of Science & Technology
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-12150
• DOI: 10.1126/science.ads4639
• 发表日期: 2025-06-19
• 关键词: group-ii intron; resistance; reveal

摘要

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.