De novo gene synthesis by an antiviral reverse transcriptase
Open accessPublished version of a preprint
Abstract
Defense-associated reverse transcriptase (DRT) systems perform DNA synthesis to protect bacteria against viral infection, but the identities and functions of their DNA products remain largely unknown. We show that DRT2 systems encode an unprecedented immune pathway that involves de novo gene synthesis through rolling circle reverse transcription of a noncoding RNA (ncRNA). Programmed template jumping on the ncRNA generates a concatemeric cDNA, which becomes double-stranded upon viral infection. This DNA product constitutes a protein-coding, nearly endless open reading frame ( neo ) gene whose expression leads to potent cell growth arrest, restricting the viral infection. Our work highlights an elegant expansion of genome coding potential through RNA-templated gene creation and challenges conventional paradigms of genetic information encoded along the one-dimensional axis of genomic DNA.
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Cites
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ColabFold - Making protein folding accessible to all
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Engineered retrons generate genome-independent protein-binding DNA for cellular control
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- Authors
- Tang, S., Conte, V., Zhang, D. J., Žedaveinytė, R., Lampe, G. D., Wiegand, T., Tang, L. C., Wang, M., Walker, M. W. G., George, J. T., Berchowitz, L. E., Jovanovic, M., & Sternberg, S. H.
- Affiliations
- Columbia University (US)
- Department of Biological Sciences, Columbia University, New York, NY, USA.
- Corresponding author
- Sternberg, Samuel H.
- ORCID
- Venue
- Science
- Published
- 2024-10-04
- Volume
- 386
- Issue
- 6717
- Pages
- eadq0876-eadq0876
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC11758365
- OpenAlex
- W4401415626
- Cited by
- 58
- References
- 5
- Citations by year
- 2026: 26 · 2025: 21 · 2024: 11
- FWCI
- 15.91
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Science (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- PubMed Central (submittedVersion, cc-by)
- Funders
- National Science Foundation (2224211)
- National Institutes of Health (1f30ai183830-01, 2224211)
- Irving Medical Center, Columbia University
- National Institute on Aging (R01AG071869)
- National Human Genome Research Institute (DP2HG011650, R01HG012216, RM1HG009490)
- National Institute of General Medical Sciences (T32GM145440, R35GM124633)
- National Institute of Allergy and Infectious Diseases (F30 AI183830, R21AI168976)
- Topics
- Physical Sciences › Environmental Science › Ecology › Bacteriophages and microbial interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Keywords
- non-coding RNA, neo gene, antiviral immunity, bacterial defense against viruses, open reading frames
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