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TitleStructural basis of the RNA-mediated Retron-Eco2 oligomerization.
Journal, issue, pagesCell Discov, Vol. 11, Issue 1, Page 73, Year 2025
Publish dateSep 2, 2025
AuthorsYanjing Wang / Chen Wang / Yongqi Yin / Yongqing Cui / Zhikang Dai / Chang Liu / Yanke Chen / Zeyuan Guan / Tingting Zou /
PubMed AbstractIn the evolutionary arms race between bacteria and viruses, retrons have emerged as distinctive antiphage defense systems. Here, we elucidate the structure and function of Retron-Eco2, which ...In the evolutionary arms race between bacteria and viruses, retrons have emerged as distinctive antiphage defense systems. Here, we elucidate the structure and function of Retron-Eco2, which comprises a non-coding RNA (ncRNA) that encodes multicopy single-stranded DNA (msDNA, a DNA‒RNA hybrid) and a fusion protein containing a reverse transcriptase (RT) domain and a topoisomerase-primase-like (Toprim) effector domain. The Eco2 msDNA and RT-Toprim fusion protein form a 1:1 stoichiometric nucleoprotein complex that further assembles into a trimer (msDNA:RT-Toprim ratio of 3:3) with a distinctive triangular configuration. The RNA portion of the msDNA in one protomer closely intertwines around the RT domain of an adjacent protomer, mediating the formation of this self-inhibitory assembly. Upon activation, the Toprim effector domain exhibits RNase activity, degrading RNA to arrest phage replication. We further reveal that phage mutants evading Eco2-mediated defense harbor mutations in the endonuclease IV-like protein DenB, underscoring DenB's critical role in triggering the activation of this system. Together, these findings provide key structural and functional insights into Retron-Eco2, laying the groundwork for harnessing its potential in biotechnology and synthetic biology applications.
External linksCell Discov / PubMed:40897710 / PubMed Central
MethodsEM (single particle)
Resolution2.6 Å
Structure data

63214

9lm3

EMDB-63214, PDB-9lm3:
cryo-EM structure of retron Eco2
Method: EM (single particle) / Resolution: 2.6 Å

Source
  • escherichia coli (E. coli)
KeywordsRNA BINDING PROTEIN/DNA/RNA / RNA-mediated retron Eco2 oligomerization / RNA BINDING PROTEIN-DNA-RNA complex

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