De novo gene synthesis by an antiviral reverse transcriptase

Science. 2024 Oct 4;386(6717):eadq0876. doi: 10.1126/science.adq0876. Epub 2024 Oct 4.

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.

MeSH terms

  • DNA, Complementary* / biosynthesis
  • DNA, Complementary* / genetics
  • Klebsiella pneumoniae* / enzymology
  • Klebsiella pneumoniae* / genetics
  • Klebsiella pneumoniae* / virology
  • Open Reading Frames
  • RNA, Untranslated* / genetics
  • RNA, Untranslated* / metabolism
  • RNA-Directed DNA Polymerase* / genetics
  • RNA-Directed DNA Polymerase* / metabolism
  • Reverse Transcription*
  • Siphoviridae* / genetics
  • Siphoviridae* / growth & development
  • Templates, Genetic

Substances

  • DNA, Complementary
  • RNA, Untranslated
  • RNA-Directed DNA Polymerase