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

Autor: Koopal B; Laboratory of Biochemistry, Wageningen University, 6708 WE Wageningen, the Netherlands., Potocnik A; Laboratory of Biochemistry, Wageningen University, 6708 WE Wageningen, the Netherlands., Mutte SK; Laboratory of Biochemistry, Wageningen University, 6708 WE Wageningen, the Netherlands., Aparicio-Maldonado C; Department of Bionanoscience, Delft University of Technology, 2629 HZ Delft, the Netherlands; Kavli Institute of Nanoscience, 2629 HZ Delft, the Netherlands., Lindhoud S; Laboratory of Biochemistry, Wageningen University, 6708 WE Wageningen, the Netherlands., Vervoort JJM; Laboratory of Biochemistry, Wageningen University, 6708 WE Wageningen, the Netherlands., Brouns SJJ; Department of Bionanoscience, Delft University of Technology, 2629 HZ Delft, the Netherlands; Kavli Institute of Nanoscience, 2629 HZ Delft, the Netherlands., Swarts DC; Laboratory of Biochemistry, Wageningen University, 6708 WE Wageningen, the Netherlands. Electronic address: daan.swarts@wur.nl.
Jazyk: angličtina
Zdroj: Cell [Cell] 2022 Apr 28; Vol. 185 (9), pp. 1471-1486.e19. Date of Electronic Publication: 2022 Apr 04.
DOI: 10.1016/j.cell.2022.03.012
Abstrakt: 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.
Competing Interests: Declaration of interests D.C.S., B.K., and A.P. have submitted a patent application regarding the utilization of short pAgo systems for NA detection.
(Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE