Phage tRNAs evade tRNA-targeting host defenses through anticodon loop mutations

Abstract

Abstract tRNAs in bacteriophage genomes are widespread across bacterial genera, but their exact function has remained unclear for more than 50 years. Multiple hypotheses have been proposed, with the most established being codon compensation, where codons more rarely used by the host but necessary for the phage are supplemented by tRNAs encoded by the phage. Here, we combine several observations and propose a new hypothesis that phage-encoded tRNAs are a means to counteract the tRNA-depleting strategies of the host to defend from viral infection. Based on mutational patterns of tRNA anticodon loops, we predict that phage tRNAs are insensitive to the host tRNAses. For tRNAs targeted in the anticodon itself, we observe phage counter-selection of targeted isoacceptor tRNAs, further supporting the hypothesis that phage tRNAs are selected to be insensitive to host anticodon nucleases. Importance The presence of tRNAs in phages was discovered more than 50 years ago and their function has been debated ever since. Here, we propose that phage tRNAs counteract the tRNAse activities of the host, which may represent a depletion strategy of essential cellular components to stop translation and thereby phage infection.