A recent study from Bluetools partners at the CSIC-INTA and Universidad Autónoma de Madrid, published in Scientific Reports, reveals that a single molecule of bacterial origin — queuosine (Q) — may play a critical role in regulating gene expression in eukaryotes.
Queuosine is a modified nucleoside found in transfer RNA (tRNA), the molecule responsible for translating genetic instructions into proteins. Despite acting on just this one codon type, Q’s effect cascades through the cell, impacting a wide range of biological processes.
Using bioinformatics, the researchers analysed the genomes of a wide range of eukaryotic organisms to predict which genes are most affected by the presence or absence of Q, referred to as Q-genes. These genes were found to be involved in essential cellular functions, including ubiquitination, splicing, DNA repair, cell cycle regulation, and phosphatidylinositol metabolism.
While the specific Q-genes vary from species to species, this study provides, for the first time, a unifying mechanism that explains the diverse physiological effects previously observed across many organisms, including development in D. discoideum and D. melanogaster, energy metabolism and stress responses in mice, and protein processing or cell adhesion in humans.
To test their predictions, the team also examined human cancer cells, where they found that queuosine availability directly affected the expression of two key genes: p53 and Akt, both of which are central to cell survival, proliferation, and DNA damage response. Although a deficiency in Q is unlikely to cause cancer on its own, the findings suggest that it may contribute to tumour progression by weakening the cell’s control mechanisms.
The study also highlights queuosine’s potential relevance in neurological function, noting previous evidence that links Q-related protein processing to neurodegenerative diseases and cognitive performance in rodents, with similar effects potentially present in humans.
What makes these findings even more intriguing is that eukaryotes cannot produce queuosine themselves; they rely entirely on salvaging it from bacteria in their environment or diet. This dependence suggests that changes in microbiome composition, or the absence of bacteria altogether, such as in germ-free organisms or cell cultures, could significantly impact gene expression by disrupting Q-genes regulation. In light of this, the authors argue that queuosine should be considered an essential nutrient, not just for its biochemical role, but for its potential to fine-tune a wide array of vital physiological processes.
You can read the full study here: https://www.nature.com/articles/s41598-024-83451-y