Decoding the general role of tRNA queuosine modification in eukaryotes

Transfer RNA (tRNA) contains modified nucleosides essential for modulating protein translation. One of these modifications is queuosine (Q), which affects NAU codons translation rate. For decades, multiple studies have reported a wide variety of species-specific Q-related phenotypes in different eukaryotes, hindering the identification of a general underlying mechanism behind that phenotypic diversity. Here, through bioinformatics analysis of representative eukaryotic genomes we have predicted: i) the genes enriched in NAU codons, whose translation would be affected by tRNA Q-modification (Q-genes); and ii) the specific biological processes of each organism enriched in Q-genes, which generally in eukaryotes would be related to ubiquitination, phosphatidylinositol metabolism, splicing, DNA repair or cell cycle. These bioinformatics results provide evidence to support for the first time in eukaryotes that the wide diversity of phenotypes associated with tRNA Q-modification previously described in various species would directly depend on the control of Q-genes translation, and would allow prediction of unknown Q-dependent processes, such as Akt activation and p53 expression, which we have tested in human cancer cells. Considering the relevance of the Q-related processes, our findings may support further exploration of the role of Q in cancer and other pathologies. Moreover, since eukaryotes must salvage Q from bacteria, we suggest that changes in Q supply by the microbiome would affect the expression of host Q-genes, altering its physiology.