A recent paper published in Nucleic Acids Research, from Western University in collaboration with BSI, highlights that naturally occurring human tRNA variants can drive systematic mistranslation in healthy cells, at levels that are high enough to matter for how we interpret proteomic data.

Rozik et al. measure mistranslation levels caused by a naturally occurring human tRNA anticodon variant, present in about 2% of the population, that introduces serine incorporation at phenylalanine codons. To do this, the authors introduced a clever dual GFP–mCherry reporter that converts translational errors into a quantitative fluorescent signal in live cells. By coupling GFP (as a production control) with a mistranslation-sensitive mCherry variant, amino acid mis-incorporation events in living human and mouse cells were detected and quantified. Using this reporter, the team showed that a single-nucleotide change (G35A) in a serine tRNA anticodon causes serine to be incorporated at phenylalanine codons—a clear violation of the canonical genetic code.

Importantly, this effect was confirmed using mass spectrometry, validating that the observed fluorescence directly reflects mistranslated protein. To support their work, the study also examined β-lymphocyte cell lines from the 1000 Genomes Project, enabling them to sample genetic diversity across the human population. Cells carrying the G35A allele not only expressed the mutant tRNA but consistently showed elevated mistranslation signals using the live-cell reporter—something not observed in cells with the wild-type tRNA.

These findings challenge the long-held assumption that healthy human cells strictly adhere to an error-free genetic code. Instead, they suggest that mistranslation is tolerated in humans, reshaping how we think about translation fidelity and protein quality control. BSI is proud to support and collaborate with academic and research partners on work that advances our understanding of human genetic and proteomic diversity and its functional impact.

Read the full article here: Rozik, P., Moore, H., Lant, J. T., Hoffman, K. S., Schultz, S. K., Afzal, B., Chan, P. P., Flynn, L. E., Heinemann, I. U., Lowe, T. M., O’Donoghue, P. (2026) Mistranslation from an endogenous tRNA variant in human pan-genome cell lines. Nucleic Acids Res. 54(5). doi:10.1093/nar/gkag224