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Cited by 53RNA and protein synthesis mechanismsBacteriophages and microbial interactionsRNA modifications and cancer

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A viral ADP-ribosyltransferase attaches RNA chains to host proteins

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Wolfram-Schauerte, Maik, Pozhydaieva, Nadiia, Grawenhoff, Julia, Welp, Luisa M., Silbern, Ivan, Wulf, Alexander, Billau, Franziska A., Glatter, Timo, Urlaub, Henning, Jäschke, Andres, Höfer, Katharina·2023·Nature
DOI 10.1038/s41586-023-06429-2PMC PMC10468400

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Abstract

The mechanisms by which viruses hijack the genetic machinery of the cells they infect are of current interest. When bacteriophage T4 infects Escherichia coli , it uses three different adenosine diphosphate (ADP)-ribosyltransferases (ARTs) to reprogram the transcriptional and translational apparatus of the host by ADP-ribosylation using nicotinamide adenine dinucleotide (NAD) as a substrate 1,2 . NAD has previously been identified as a 5′ modification of cellular RNAs 3–5 . Here we report that the T4 ART ModB accepts not only NAD but also NAD-capped RNA (NAD–RNA) as a substrate and attaches entire RNA chains to acceptor proteins in an ‘RNAylation’ reaction. ModB specifically RNAylates the ribosomal proteins rS1 and rL2 at defined Arg residues, and selected E. coli and T4 phage RNAs are linked to rS1 in vivo. T4 phages that express an inactive mutant of ModB have a decreased burst size and slowed lysis of E. coli . Our findings reveal a distinct biological role for NAD–RNA, namely the activation of the RNA for enzymatic transfer to proteins. The attachment of specific RNAs to ribosomal proteins might provide a strategy for the phage to modulate the host’s translation machinery. This work reveals a direct connection between RNA modification and post-translational protein modification. ARTs have important roles far beyond viral infections 6 , so RNAylation may have far-reaching implications.

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Metadata

Authors
Wolfram-Schauerte, M., Pozhydaieva, N., Grawenhoff, J., Welp, L. M., Silbern, I., Wulf, A., Billau, F. A., Glatter, T., Urlaub, H., Jäschke, A., & Höfer, K.
Affiliations
  • Heidelberg University (DE)
  • Max Planck Institute for Terrestrial Microbiology (DE)
  • Universitätsmedizin Göttingen (DE)
  • Max Planck Institute for Multidisciplinary Sciences (DE)
  • Philipps University of Marburg (DE)
Corresponding author
  • Jäschke, Andres
  • Höfer, Katharina
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2023-08-16
Volume
620
Issue
7976
Pages
1054-1062
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/s41586-023-06429-2
PMC
PMC10468400
OpenAlex
W4385879373
Cited by
53
References
1
Citations by year
2026: 15 · 2025: 12 · 2024: 19 · 2023: 2
FWCI
4.26
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • GoeScholar The Publication Server of the Georg-August-Universität Göttingen (Georg-August-Universität Göttingen) (submittedVersion, cc-by)
Funders
  • Carl-Zeiss-Stiftung
  • Baden-Württemberg Stiftung
  • Joachim Herz Stiftung
  • European Commission (HORIZON2020)
  • Deutsche Forschungsgemeinschaft (TRR319, SPP‐1935, 469281184, project A02, 439669440, SFB1286, SFB1565, SPP2330)
  • Max-Planck-Gesellschaft
  • Studienstiftung des Deutschen Volkes
  • H2020 European Research Council (882789)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Immunology and Microbiology › Virology › Bacteriophages and microbial interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
Keywords
ADP-ribosyltransferase, bacteriophage T4, post-translational protein modification, phage burst size, Escherichia coli
MeSH terms
Escherichia coli, NAD, Protein Processing, Post-Translational, Ribosomal Proteins, RNA, Protein Biosynthesis, Viral Proteins, Gene Expression Regulation, Bacterial, Bacteriophage T4, Escherichia coli Proteins, ADP Ribose Transferases

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