Structure and mechanism of antiphage retron Eco2

Retrons are prokaryotic reverse transcriptase systems that produce multicopy single-stranded DNA (msDNA), yet the principles by which they mediate antiviral defense remain largely unresolved. Here we investigate the mechanism of Escherichia coli Eco2, a minimal retron composed of a single reverse transcriptase-nuclease fusion protein. Cryogenic electron microscopy and hydrogen/deuterium exchange mass spectrometry reveal the structures and dynamics of a trimeric nucleoprotein complex assembled within a branched msDNA scaffold, which cages the TOPRIM nucleases. We show that the phage-encoded endonuclease DenB initiates msDNA degradation, thereby unblocking the nuclease active sites. Activated Eco2 cuts transfer RNAs, resulting in translational shutdown for antiphage defense. We further identify ribosomal protein S1 as a putative RNA chaperone that associates with the msDNA precursor. These findings provide insights into the molecular mechanisms of minimal retrons and establish a structural basis for engineering of Eco2.

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Publication Details

Journal
Nature Structural & Molecular Biology
Published
2026-02-01
DOI
https://doi.org/10.1038/s41594-026-01754-2
Citations
1
Primary Topic
RNA and protein synthesis mechanisms
Type
article
Field-Weighted Citation Impact
22.24
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Structure and mechanism of antiphage retron Eco2

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Nature Structural & Molecular Biology
RNA and protein synthesis mechanisms
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Structure and mechanism of antiphage retron Eco2

Inga Songailienė, J. Juozapaitis, A. Skorupskaitė, Lidija Truncaitė, Patrick Pausch, L. Malinauskaitė, Rokas Grigaitis, Algirdas Mikšys, Monika Jasnauskaitė, Wieland Steinchen, Kristina Kazlauskaitė, Sharvika Khochare, Toma Liegutė, Gert Bange, G. Dudas, M. F. Torres Jiménez
article en
1 citations

Abstract

Retrons are prokaryotic reverse transcriptase systems that produce multicopy single-stranded DNA (msDNA), yet the principles by which they mediate antiviral defense remain largely unresolved. Here we investigate the mechanism of Escherichia coli Eco2, a minimal retron composed of a single reverse transcriptase-nuclease fusion protein. Cryogenic electron microscopy and hydrogen/deuterium exchange mass spectrometry reveal the structures and dynamics of a trimeric nucleoprotein complex assembled within a branched msDNA scaffold, which cages the TOPRIM nucleases. We show that the phage-encoded endonuclease DenB initiates msDNA degradation, thereby unblocking the nuclease active sites. Activated Eco2 cuts transfer RNAs, resulting in translational shutdown for antiphage defense. We further identify ribosomal protein S1 as a putative RNA chaperone that associates with the msDNA precursor. These findings provide insights into the molecular mechanisms of minimal retrons and establish a structural basis for engineering of Eco2.

Nature Structural & Molecular BiologyVol. 33(2)
University of Copenhagen (DK), MRC Laboratory of Molecular Biology (GB), Vilnius University (LT), Novo Nordisk Foundation (DK), Vilnius College of Technologies and Design (LT), Academy of Arts Education (DE), Loewe Center for Synthetic Microbiology (DE), Max Planck Institute for Terrestrial Microbiology (DE)
Openalex Percentile: Top 1%
RNA and protein synthesis mechanisms
22.24
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