Figure 3.

Modeling the impact of regulating translation kinetics. The kinetics of translation along an mRNA transcript is nonuniform and balanced between ribosome pausing and acceleration. In homeostatic conditions in the cell, this balance is optimized for proper folding of the nascent proteome. Deviation from this balance decreases the likelihood of folding and impacts the fate of the protein: Aberrantly fast translation leads to misfolding and aggregation, and aberrantly slow translation leads to protein and mRNA turnover. The details that define the probability distribution of protein folding will change in response to changing cellular environments. For instance, alterations in the tRNA pool will influence what codons are considered optimal versus nonoptimal, which subsequently impacts protein folding.