Quantifying the benefits of translation regulation in the unfolded protein response.

Protein production can be regulated at the translation stage through modulation of mRNA activity and degradation. In the unfolded protein response in S. cerevisiae it works by regulating the conversion rate from a reservoir of passive mRNA to an active short-lived mRNA that is open for translation. We develop a mathematical model for translation regulation, and elucidate its properties in perspective of the size and timing of the unfolded protein response. Optimal response is obtained when active mRNA has high decay rate compared to both the conversion rate and the decay rate of passive mRNA. In that case the translation regulation can provide the observed pulse of chaperones that fast restore protein folding conditions in the endoplasmic reticulum. Finally, we discuss translation control in relation to other known mechanisms for stress responses. Feedback on the translation level is found to be superior to transcription when conditions necessitate a fast shift in protein concentration while retaining a small cost in terms of protein degradation.