The Dynamics of Supply and Demand in mRNA Translation

We study the elongation stage of mRNA translation in eukaryotes and find that, in contrast to the assumptions of previous models, both the supply and the demand for tRNA resources are important for determining elongation rates. We find that increasing the initiation rate of translation can lead to the depletion of some species of aa-tRNA, which in turn can lead to slow codons and queueing. Particularly striking “competition” effects are observed in simulations of multiple species of mRNA which are reliant on the same pool of tRNA resources. These simulations are based on a recent model of elongation which we use to study the translation of mRNA sequences from the Saccharomyces cerevisiae genome. This model includes the dynamics of the use and recharging of amino acid tRNA complexes, and we show via Monte Carlo simulation that this has a dramatic effect on the protein production behaviour of the system. Author Summary: In this paper we show that the rate at which proteins are produced can be controlled at the elongation stage of mRNA translation. Regulation of translation initiation has been a focus of much study, but the subsequent effect of changes in the initiation rate on the overall translation rate, and the role of slow and fast codon usage in mRNA sequences is still not fully understood. We consider a model of elongation in which the dynamics of tRNA use and recharging are considered for real mRNA sequences. We find that the balance between the demand for, and supply of tRNAs is crucial in determining translation rates. Particularly interesting “competition” effects are observed when the simultaneous translation of multiple mRNA is considered. We show indeed that, via the choice of slow or fast codons, it is in principle possible to control how variation of the supply and demand for tRNA resources changes the rate of protein production from different mRNAs.