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TitleBacterial reverse transcriptase synthesizes long poly(A)-rich cDNA for antiphage defense.
Journal, issue, pagesScience, Vol. 388, Issue 6753, Page eads4639, Year 2025
Publish dateJun 19, 2025
AuthorsXin-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 /
PubMed AbstractProkaryotic defense-associated reverse transcriptases (DRTs) were recently identified with antiviral functions; however, their functional mechanisms remain largely unexplored. Here we show that DRT9 ...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.
External linksScience / PubMed:40310939
MethodsEM (single particle)
Resolution2.59 - 2.62 Å
Structure data

60724

9ioa

EMDB-60724, PDB-9ioa:
Cryo-EM structure of the tetrameric DRT9-ncRNA complex
Method: EM (single particle) / Resolution: 2.59 Å

60725

9iob

EMDB-60725, PDB-9iob:
Cryo-EM structure of the hexameric DRT9-ncRNA complex
Method: EM (single particle) / Resolution: 2.62 Å

Source
  • escherichia coli (E. coli)
KeywordsANTIVIRAL PROTEIN/RNA / RNA BINDING / PROTEIN-RNA COMPLEX / ANTIVIRAL PROTEIN-RNA complex

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