Raué H A
Department of Biochemistry and Molecular Biology, BioCentrum Amsterdam, Vrije Universiteit, The Netherlands.
Trends Biotechnol. 1994 Nov;12(11):444-9. doi: 10.1016/0167-7799(94)90019-1.
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.
迄今为止，为提高酵母细胞中（异源）蛋白质的产量所做的尝试几乎完全集中在通过增加每个细胞中的基因拷贝数，和/或将基因置于强同源启动子的控制之下，来提高异源基因的转录产量。然而，可翻译mRNA的细胞水平是其产生速率以及被核酸降解去除——或至少失活——的速率的函数。最近，在阐明酵母细胞中mRNA衰变机制以及鉴定参与此过程的顺式作用稳定性决定因素和反式作用因子方面取得了相当大的进展。这些知识可作为对给定转录本进行合理工程改造的基础，以调节其代谢稳定性，进而调节其细胞水平。
