Phage tRNAs evade tRNA-targeting host defenses through anticodon loop mutations
Abstract
tRNAs in bacteriophage genomes are widespread across bacterial host genera, but their exact function has remained unclear for more than 50 years. Several hypotheses have been proposed, and the most widely accepted one is codon compensation, which suggests that phages encode tRNAs that supplement codons that are less frequently used by the host. Here, we combine several observations and propose a new hypothesis that phage-encoded tRNAs counteract the tRNA-depleting strategies of the host using enzymes such as VapC, PrrC, Colicin D, and Colicin E5 to defend from viral infection. Based on mutational patterns of anticodon loops of tRNAs encoded by phages, we predict that these tRNAs are insensitive to host tRNAses. For phage-encoded tRNAs targeted in the anticodon itself, we observe that phages typically avoid encoding these tRNAs. Further supporting the hypothesis that phage tRNAs are selected to be insensitive to host anticodon nucleases. Altogether our results support the hypothesis that phage-encoded tRNAs have evolved to be insensitive to host anticodon nucleases.
Data availability
An overview of the analysed data supporting the findings of this study are available within the paper and in the Supplementary Data. All genomic sequences of the C1 mycobacteriophages were obtained from the publicly available actinobacteriophage database (PhagesDB; link: https://phagesdb.org/subclusters/C1/). Mycobacterium smegmatis MC2-155 (CP000480.1) and Mycobacterium tuberculosis H37Rv (NC_000962.3) were used as reference for the obtaining the host tRNA sequences.
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PhagesDB: the actinobacteriophage databasePhagesDB: the actinobacteriophage database, doi: 10.1093/bioinformatics/btw711.
Article and author information
Author details
Funding
European Research Council (101003229)
- Daan F van den Berg
- Baltus A van der Steen
- Ana Rita Costa
- Stan JJ Brouns
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Ruben L Gonzalez, Columbia University, United States
Version history
- Preprint posted: November 9, 2022 (view preprint)
- Received: November 25, 2022
- Accepted: June 1, 2023
- Accepted Manuscript published: June 2, 2023 (version 1)
- Version of Record published: June 13, 2023 (version 2)
Copyright
© 2023, van den Berg et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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