Structural basis of antiphage defence by an ATPase-associated reverse transcriptase
Reverse transcriptases (RTs) have well-established roles in the replication and spread of retroviruses and retrotransposons. However, recent evidence suggests that RTs have been conscripted by cells for diverse roles in antiviral defence. Here we determine structures of a type I-A retron, which explain how RNA, DNA, RT, HNH-nuclease and four molecules of a structure maintenance of chromosome (SMC)-family ATPase assemble into a 364 kDa complex that provides phage defence. We show that phage-encoded nucleases trigger degradation of the retron-associated DNA, leading to activation of the HNH nuclease. The HNH nuclease cleaves tRNA<sub>Ser</sub>, stalling protein synthesis and arresting viral replication. Taken together, these data reveal diverse and paradoxical roles for RTs in the perpetuation and elimination of genetic parasites.
Authors
- Ann Marie Dale (ORCID: https://orcid.org/0000-0002-5624-8967)
- Ava B. Graham (ORCID: https://orcid.org/0000-0002-6782-5248)
- Blake Wiedenheft (ORCID: https://orcid.org/0000-0001-9297-5304)
- Murat Buyukyoruk (ORCID: https://orcid.org/0000-0003-1534-7202)
- Nathaniel Burman (ORCID: https://orcid.org/0000-0002-3732-3159)
- Steven Z. DeLuca (ORCID: https://orcid.org/0000-0003-0683-8413)
- Senuri de Silva (ORCID: https://orcid.org/0000-0002-9870-4449)
- Royce A. Wilkinson (ORCID: https://orcid.org/0000-0001-8831-2081)
- Jerrin Thomas George (ORCID: https://orcid.org/0000-0001-9696-0564)
- Quynh McKelvey-Pham
- Hannah Landman
Institutions
- Montana State University (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-09-26
- DOI
- https://doi.org/10.1038/s41467-025-63285-6
- Citations
- 7
- Primary Topic
- RNA modifications and cancer
- Type
- article
- Field-Weighted Citation Impact
- 5.64
Funders
- National Science Foundation
- U.S. Department of Agriculture
- M.J. Murdock Charitable Trust
- Montana State University
- National Institutes of Health
- National Institute of Food and Agriculture
- University of California, San Francisco
- National Institute of Allergy and Infectious Diseases