Lifestyle modifications: coordinating the tRNA epitranscriptome with codon bias to adapt translation during stress responses

Cells adapt to stress by altering gene expression at multiple levels. Here, we propose a new mechanism regulating stress-dependent gene expression at the level of translation, with coordinated interplay between the tRNA epitranscriptome and biased codon usage in families of stress-response genes. In this model, auxiliary genetic information contained in synonymous codon usage enables regulation of codon-biased and functionally related transcripts by dynamic changes in the tRNA epitranscriptome. This model partly explains the association between synchronous stress-dependent epitranscriptomic marks and significant multi-codon usage skewing in families of translationally regulated transcripts. The model also predicts translational adaptation during viral infections.