Klein C, Struhl K
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115.
Mol Cell Biol. 1994 Mar;14(3):1920-8. doi: 10.1128/mcb.14.3.1920-1928.1994.
Yeast ribosomal protein genes are coordinately regulated as a function of cell growth; RNA levels decrease during amino acid starvation but increase following a carbon source upshift. Binding sites for RAP1, a multifunctional transcription factor, are present in nearly all ribosomal protein genes and are associated with growth rate regulation. We show that ribosomal protein mRNA levels are increased twofold in strains that have constitutively high levels of cyclic AMP-dependent protein kinase (protein kinase A [PKA]) activity. The PKA-dependent induction requires RAP1 binding sites, and it reflects increased transcriptional activation by RAP1. Growth-regulated transcription of ribosomal protein genes strongly depends on the ability to regulate PKA activity. Cells with constitutively high PKA levels do not show the transcriptional decrease in response to amino acid starvation. Conversely, in cells with constitutively low PKA activity, ribosomal protein mRNAs levels are lower and largely uninducible upon carbon source upshift. We suggest that modulation of RAP1 transcriptional activity by PKA accounts for growth-regulated expression of ribosomal protein genes.
酵母核糖体蛋白基因作为细胞生长的一个功能被协同调节；在氨基酸饥饿期间RNA水平下降，但在碳源上调后增加。RAP1是一种多功能转录因子，几乎所有核糖体蛋白基因中都存在其结合位点，且这些位点与生长速率调节相关。我们发现，在组成型具有高水平环腺苷酸依赖性蛋白激酶（蛋白激酶A [PKA]）活性的菌株中，核糖体蛋白mRNA水平增加了两倍。PKA依赖性诱导需要RAP1结合位点，这反映了RAP1转录激活作用的增强。核糖体蛋白基因的生长调节转录强烈依赖于调节PKA活性的能力。组成型具有高PKA水平的细胞在氨基酸饥饿时不会出现转录下降。相反，在组成型具有低PKA活性的细胞中，核糖体蛋白mRNA水平较低，并且在碳源上调时基本不可诱导。我们认为PKA对RAP1转录活性的调节作用解释了核糖体蛋白基因的生长调节表达。
