Wittekind M, Kolb J M, Dodd J, Yamagishi M, Mémet S, Buhler J M, Nomura M
Department of Biological Chemistry, University of California, Irvine 92717.
Mol Cell Biol. 1990 May;10(5):2049-59. doi: 10.1128/mcb.10.5.2049-2059.1990.
The synthesis of ribosomal proteins (r proteins) under the conditions of greatly reduced RNA synthesis were studied by using a strain of the yeast Saccharomyces cerevisiae in which the production of the largest subunit (RPA190) of RNA polymerase I was controlled by the galactose promoter. Although growth on galactose medium was normal, the strain was unable to sustain growth when shifted to glucose medium. This growth defect was shown to be due to a preferential decrease in RNA synthesis caused by deprivation of RNA polymerase I. Under these conditions, the accumulation of r proteins decreased to match the rRNA synthesis rate. When proteins were pulse-labeled for short periods, no or only a weak decrease was observed in the differential synthesis rate of several r proteins (L5, L39, L29 and/or L28, L27 and/or S21) relative to those of control cells synthesizing RPA190 from the normal promoter. Degradation of these r proteins synthesized in excess was observed during subsequent chase periods. Analysis of the amounts of mRNAs for L3 and L29 and their locations in polysomes also suggested that the synthesis of these proteins relative to other cellular proteins were comparable to those observed in control cells. However, Northern analysis of several r-protein mRNAs revealed that the unspliced precursor mRNA for r-protein L32 accumulated when rRNA synthesis rates were decreased. This result supports the feedback regulation model in which excess L32 protein inhibits the splicing of its own precursor mRNA, as proposed by previous workers (M. D. Dabeva, M. A. Post-Beittenmiller, and J. R. Warner, Proc. Natl. Acad. Sci. USA 83:5854-5857, 1986).
通过使用酿酒酵母菌株,研究了在RNA合成大幅减少的条件下核糖体蛋白(r蛋白)的合成。在该菌株中,RNA聚合酶I最大亚基(RPA190)的产生由半乳糖启动子控制。尽管在半乳糖培养基上生长正常,但该菌株转移到葡萄糖培养基后无法维持生长。结果表明,这种生长缺陷是由于RNA聚合酶I缺失导致RNA合成优先减少所致。在这些条件下,r蛋白的积累减少以匹配rRNA合成速率。当对蛋白质进行短时间脉冲标记时,相对于从正常启动子合成RPA190的对照细胞,几种r蛋白(L5、L39、L29和/或L28、L27和/或S21)的差异合成速率没有降低或仅略有降低。在随后的追踪期内观察到这些过量合成的r蛋白发生降解。对L3和L29的mRNA量及其在多核糖体中的位置进行分析,也表明这些蛋白质相对于其他细胞蛋白的合成与对照细胞中观察到的情况相当。然而,对几种r蛋白mRNA的Northern分析显示,当rRNA合成速率降低时,r蛋白L32的未剪接前体mRNA会积累。这一结果支持了先前研究人员提出的反馈调节模型,即过量的L32蛋白会抑制其自身前体mRNA的剪接(M. D. Dabeva、M. A. Post-Beittenmiller和J. R. Warner,《美国国家科学院院刊》83:5854 - 5857,1986)。