De novo gene synthesis by an antiviral reverse transcriptase

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. Here we show that DRT2 systems encode an unprecedented immune pathway that involves de novo gene sy...

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Published inScience (American Association for the Advancement of Science) p. eadq0876
Main Authors Tang, Stephen, Conte, Valentin, Zhang, Dennis J, Žedaveinytė, Rimantė, Lampe, George D, Wiegand, Tanner, Tang, Lauren C, Wang, Megan, Walker, Matt W G, George, Jerrin Thomas, Berchowitz, Luke E, Jovanovic, Marko, Sternberg, Samuel H
Format Journal Article
LanguageEnglish
Published United States 08.08.2024
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Summary: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. Here we show that DRT2 systems encode an unprecedented immune pathway that involves de novo gene synthesis via rolling circle reverse transcription of a non-coding RNA (ncRNA). Programmed template jumping on the ncRNA generates a concatemeric cDNA, which becomes double-stranded upon viral infection. Remarkably, this DNA product constitutes a protein-coding, nearly endless ORF ( ) gene whose expression leads to potent cell growth arrest, thereby 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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ISSN:0036-8075
1095-9203
1095-9203
DOI:10.1126/science.adq0876