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

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Short prokaryotic Argonautes provide defence against incoming mobile genetic elements through NAD + depletion

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Zaremba, Mindaugas, Dakineviciene, Donata, Golovinas, Edvardas, Zagorskaitė, Evelina, Stankunas, Edvinas, Lopatina, Anna, Sorek, Rotem, Manakova, Elena, Ruksenaite, Audrone, Silanskas, Arunas, Asmontas, Simonas, Grybauskas, Algirdas, Tylenyte, Ugne, Jurgelaitis, Edvinas, Grigaitis, Rokas, Timinskas, Kęstutis, Venclovas, Česlovas, Siksnys, Virginijus·2021·Nature Microbiology
DOI 10.1101/2021.12.14.472599

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

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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). The majority (~60%) of 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 Geobacter sulfurreducens short pAgo and the NAD + -bound Sir2-protein form a stable heterodimeric complex. The GsSir2/Ago complex presumably recognizes invading plasmid or phage DNA and activates the Sir2 subunit, which triggers endogenous NAD + depletion and cell death, and prevents the propagation of invading DNA. We reconstituted NAD + depletion activity in vitro and showed that activated GsSir2/Ago complex functions as a NADase that hydrolyses NAD + to ADPR. Thus, short Sir2-associated pAgos provide defence against phages and plasmids and underscores the diversity of mechanisms of prokaryotic Agos.

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Metadata

Authors
Zaremba, M., Dakineviciene, D., Golovinas, E., Zagorskaitė, E., Stankunas, E., Lopatina, A., Sorek, R., Manakova, E., Ruksenaite, A., Silanskas, A., Asmontas, S., Grybauskas, A., Tylenyte, U., Jurgelaitis, E., Grigaitis, R., Timinskas, K., Venclovas, Č., & Siksnys, V.
Affiliations
  • Vilnius University (LT)
  • University of Vienna (AT)
  • Weizmann Institute of Science (IL)
Corresponding author
Zaremba, Mindaugas
ORCID
Venue
Nature Microbiology
Publisher
openRxiv
Published
2021-12-14
Volume
7
Issue
11
Pages
1857-1869
ISSN
2058-5276 (ISSN-L)
DOI
10.1101/2021.12.14.472599
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
Licence
cc-by-nc-nd
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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