Development of a deterministic mathematical model of translation termination. Parameters were assigned to a deterministic model of translation, incorporating a description of termination, using a staged series of models of increasing complexity. (A) In each case, the complete translation process was divided into a series of modules that described a coarse-grained, or “lumped” model of the multistep translation process. (B) Parameters associated with eRF1 synthesis were fitted using a simple Model 1 of eRF1 mRNA translation. (C) The parameters describing release factor recognition of the stop codon and of the competition between release factor and suppressor tRNA were optimized using a more complex Model 2 in which an mRNA containing a premature stop codon is translated to produce a generic protein X. (D) A final Model 3, in which the eRF1 mRNA with a premature stop codon is translated, thus describing a negative feedback loop, was used to simulate expression of eRF1 in a cell carrying a sup45 nonsense allele.
