PreprintCited by 126CRISPR and Genetic EngineeringBacterial Genetics and BiotechnologyBacteriophages and microbial interactions

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

Sir2-domain associated short prokaryotic Argonautes provide defence against invading mobile genetic elements through NAD+ depletion

Open access

Preprint — published as 10.1038/s41564-022-01239-0

Abstract

Argonaute (Ago) proteins are found in all three domains of life. The so-called long Agos are composed of four major domains (N, PAZ, MID, and PIWI) and contribute to RNA silencing in eukaryotes (eAgos) or defence against invading mobile genetic elements in prokaryotes (pAgos). Intriguingly, the majority (~60%) of prokaryotic Agos (pAgos) identified bioinformatically are shorter (comprised of only MID and PIWI domains) and are typically associated with Sir2, Mrr or TIR domain-containing proteins. The cellular function and mechanism of short pAgos remain enigmatic. Here, we show that short pAgos from Geobacter sulfurreducens, Caballeronia cordobensis and Paraburkholderia graminis, together with the NAD+-bound Sir2-proteins form a stable heterodimeric Sir2/Ago complex that recognizes invading plasmid or phage DNA through the pAgos subunit and activates Sir2 subunit triggering the endogenous NAD+ depletion and cell death thus preventing the propagation of invading DNA. This is the first demonstration that short Sir2-associated pAgos provide defence against phages and plasmids and underscores the diversity of mechanisms of prokaryotic Agos.

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Crossref · 10.21203/rs.3.rs-1174409/v1

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Metadata

Authors
Zaremba, M., Dakineviciene, D., Golovinas, E., Stankunas, E., Lopatina, A., Sorek, R., Manakova, E., Ruksenaite, A., Silanskas, A., Ašmontas, S., Grigaitis, R., Timinskas, K., Venclovas, Č., & Siksnys, V.
Affiliations
  • Vilnius University (LT)
  • University of Vienna (AT)
  • Weizmann Institute of Science (IL)
  • Vilnius university
  • Vilnius University
Corresponding author
Zaremba, Mindaugas
Venue
Nature Microbiology
Published
2022-01-06
Volume
7
Issue
11
Pages
1857-1869
ISSN
2058-5276 (ISSN-L)
OpenAlex
W4300861916
Cited by
126
References
1
Citations by year
2026: 20 · 2025: 29 · 2024: 31 · 2023: 38 · 2022: 8
FWCI
8.65
Type
journal article
Language
en
Open access
Locations
  • Nature Microbiology (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • Research Square (acceptedVersion, cc-by)
  • PubMed (publishedVersion)
  • Desy Publications Database (Deutsches Elektronen-Synchrotron DESY) (submittedVersion)
  • DESY Publication Database (PUBDB) (Deutsches Elektronen-Synchrotron)
Funders
  • Deutsche Forschungsgemeinschaft (464312965, SPP2330)
  • Israel Science Foundation (ISF 296/21, SPP 2330)
  • Lietuvos Mokslo Taryba (09.3.3-LMT-K-712-01-0126, 09.3.3‐LMT‐K‐712, 3-LMT-K-712)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Life Sciences › Immunology and Microbiology › Virology › Bacteriophages and microbial interactions
Keywords
Sir2, Geobacter sulfurreducens, NAD+ depletion, NADase activity, phage defense, abortive infection, heterodimeric complex, mobile genetic elements, RNA silencing, cell death
MeSH terms
Bacteriophages, DNA, NAD, Prokaryotic Cells, Interspersed Repetitive Sequences, Argonaute Proteins

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