Lennon K, Bird A, Chen Y F, Pretel R, Kukuruzinska M A
Department of Biochemistry, School of Medicine, Boston University Medical Center, MA 02118, USA.
Mol Cell Biochem. 1997 Apr;169(1-2):95-106. doi: 10.1023/a:1006803004151.
The yeast ALG7 gene functions by initiating the synthesis of the dolichol-linked oligosaccharide precursor and plays an important role in the control of protein N-glycosylation. The levels of ALG7 multiple transcripts are modulated by the physiological status of the cell and environmental cues, and deregulation of their abundance is deleterious to several cellular functions. Since ALG7 mRNAs are unstable, we investigated the role of these transcripts' half-lives in determining their steady-state levels. Using a temperature-sensitive RNA polymerase II mutant, we demonstrate that increased stability was the primary determinant of higher ALG7 mRNA abundance in response to glucose limitation or treatment with tunicamycin. In contrast, at the G1/G0 transition point, changes in the decay rates were inversely related to ALG7 transcript accumulation: the decreased abundance of ALG7 mRNAs following exit from the mitotic cycle was associated with lengthening of the decay rates, while their increased accumulation after growth stimulation correlated with decreased stability. This suggests that, depending on the circumstance, mRNA half-lives can either directly determine the level of ALG7 transcript accumulation or oppose regulatory changes at other control levels.
酵母ALG7基因通过启动多萜醇连接的寡糖前体的合成发挥作用,并在蛋白质N-糖基化的控制中起重要作用。ALG7多种转录本的水平受细胞生理状态和环境信号的调节,其丰度的失调对多种细胞功能有害。由于ALG7 mRNA不稳定,我们研究了这些转录本半衰期在决定其稳态水平中的作用。使用温度敏感的RNA聚合酶II突变体,我们证明稳定性增加是响应葡萄糖限制或衣霉素处理时ALG7 mRNA丰度升高的主要决定因素。相反,在G1/G0转换点,降解速率的变化与ALG7转录本积累呈负相关:有丝分裂周期结束后ALG7 mRNA丰度降低与降解速率延长相关,而生长刺激后其积累增加与稳定性降低相关。这表明,根据具体情况,mRNA半衰期既可以直接决定ALG7转录本积累的水平,也可以在其他控制水平上对抗调节变化。