Reverse transcribed ssDNA derepresses translation of a retron antiviral protein.

Authors

Karen Zhang, Matías Rojas-Montero, Darshini Poola, Josepha M Klas, Arturo Carabias, Dennis J Zhang, Mario R Mestre, Ruiliang Zhao, Ana Dávila-Hidalgo, Lieza Chan, Kliment A Verba, Guillermo Montoya, Rafael Pinilla-Redondo, Alejandro González-Delgado, Seth L Shipman

Published in

Molecular cell. Oct 13, 2026. Epub Oct 13, 2026.

Abstract

Retrons are bacterial immune systems that prevent phage propagation by initiating a toxic response within infected hosts. Previously characterized retrons produce abundant multicopy single-stranded DNA (msDNA) by reverse transcription, which acts as an antitoxin in the absence of phage. However, we describe here a non-canonical mechanism for type VI retrons, which do not produce detectable msDNA in the absence of phage yet still provide defense. Focusing on Retron-Vpa2 from V. parahaemolyticus, we show broad defense against phages and identify triggers of the system when expressed in E. coli. Within the retron operon, we find a highly enriched, structured transcript that we term a hybrid RNA (hyRNA). The hyRNA contains the reverse transcription template and a toxin coding sequence that is repressed by a riboregulator. In our model of triggering, phage infection induces accumulation of msDNA, which hybridizes to the riboregulator and enables RNase H cleavage, derepressing translation of the toxin.

PMID:
42869009
Bibliographic data and abstract were imported from PubMed on 14 Oct 2026.

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