Short prokaryotic Argonaute systems trigger cell death upon detection of invading DNA

Balwina Koopal, Ana Potocnik, Sumanth K. Mutte, Cristian Aparicio-Maldonado, Simon Lindhoud, Jacques J.M. Vervoort, Stan J.J. Brouns, Daan C. Swarts*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

74 Citations (Scopus)

Abstract

Argonaute proteins use single-stranded RNA or DNA guides to target complementary nucleic acids. This allows eukaryotic Argonaute proteins to mediate RNA interference and long prokaryotic Argonaute proteins to interfere with invading nucleic acids. The function and mechanisms of the phylogenetically distinct short prokaryotic Argonaute proteins remain poorly understood. We demonstrate that short prokaryotic Argonaute and the associated TIR-APAZ (SPARTA) proteins form heterodimeric complexes. Upon guide RNA-mediated target DNA binding, four SPARTA heterodimers form oligomers in which TIR domain-mediated NAD(P)ase activity is unleashed. When expressed in Escherichia coli, SPARTA is activated in the presence of highly transcribed multicopy plasmid DNA, which causes cell death through NAD(P)+ depletion. This results in the removal of plasmid-invaded cells from bacterial cultures. Furthermore, we show that SPARTA can be repurposed for the programmable detection of DNA sequences. In conclusion, our work identifies SPARTA as a prokaryotic immune system that reduces cell viability upon RNA-guided detection of invading DNA.

Original languageEnglish
Pages (from-to)1471-1486
JournalCell
Volume185
Issue number9
DOIs
Publication statusPublished - 28 Apr 2022

Keywords

  • abortive infection
  • Ago
  • APAZ
  • Argonaute
  • host defense
  • prokaryotic immunity
  • RNAi
  • short pAgo
  • small RNA
  • TIR

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