Metabolic stability of mRNA in yeast--a potential target for modulating productivity?

Attempts to improve the production of (heterologous) proteins in yeast cells have, to date, focused almost exclusively on increasing the transcriptional yield of the heterologous gene by raising the number of gene copies per cell, and/or putting the gene under the control of a strong homologous promoter. However, the cellular level of translatable mRNA is a function of the rate at which it is produced and the rate at which it is removed--or at least inactivated--by nucleolytic degradation. Recently, considerable progress has been made in unravelling the mechanism of mRNA decay in yeast cells and in identifying both the cis-acting stability determinants and the trans-acting factors involved in this process. This knowledge can be used as the basis for rational engineering of a given transcript to modulate its metabolic stability, and thus its cellular level.