De novo gene synthesis by an antiviral reverse transcriptase.

Autor: Tang S; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA., Conte V; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA., Zhang DJ; Department of Biological Sciences, Columbia University, New York, NY, USA., Žedaveinytė R; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA., Lampe GD; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA., Wiegand T; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA., Tang LC; Department of Biological Sciences, Columbia University, New York, NY, USA., Wang M; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA., Walker MWG; Department of Biological Sciences, Columbia University, New York, NY, USA., George JT; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA., Berchowitz LE; Department of Genetics and Development, Columbia University, New York, NY, USA.; Taub Institute for Research on Alzheimer's and the Aging Brain, New York, NY, USA., Jovanovic M; Department of Biological Sciences, Columbia University, New York, NY, USA., Sternberg SH; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA.
Jazyk: angličtina
Zdroj: Science (New York, N.Y.) [Science] 2024 Oct 04; Vol. 386 (6717), pp. eadq0876. Date of Electronic Publication: 2024 Oct 04.
DOI: 10.1126/science.adq0876
Abstrakt: 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.
Databáze: MEDLINE
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