Pharmaceutical Sciences, School of Pharmacy, University of Wisconsin, Madison, Wisconsin 53705, USA.
Genetics. 2010 Jul;185(3):797-810. doi: 10.1534/genetics.110.116665. Epub 2010 Apr 12.
Addition of glucose to quiescent Saccharomyces cerevisiae cells causes the immediate induction of approximately 1000 genes. These genes include ribosomal proteins (RP) and non-RP genes needed for ribosome production and other growth processes. RRPE sequence elements are commonly found 5' of non-RP growth gene ORFs, and Stb3 has recently been identified as an RRPE binding protein. Stb3 overexpression (Stb3OE) produces a slow growth phenotype that is associated with reduced expression of non-RP genes and a drop in the rate of amino acid incorporation. Genes affected by Stb3 are associated with a TGAAAAA motif. Stb3 is restricted to the nucleus in quiescent cells and is immediately released into the cytoplasm after glucose repletion. The Stb3OE slow growth phenotype is reversed by loss of Hos2 histone deactylase activity, consistent with the idea that repression involves histone deacetylation. SCH9 overexpression or PPH22 deletion, mutations that activate target of rapamycin (Tor) nutrient sensing pathways, also reverse the Stb3OE phenotype. Inhibition of Tor signaling makes the phenotype more severe and restricts Stb3 to the nucleus. The results support a model in which Stb3 is one of the components that repress a large set of growth genes as nutrients are depleted. This repression is ended by glucose.
当处于静止期的酿酒酵母细胞中添加葡萄糖时,会立即诱导大约 1000 个基因的表达。这些基因包括核糖体蛋白(RP)和非 RP 基因,它们是核糖体生成和其他生长过程所必需的。RRPE 序列元件通常存在于非 RP 生长基因 ORFs 的 5'端,最近已经鉴定出 Stb3 是 RRPE 结合蛋白。Stb3 的过表达(Stb3OE)会产生生长缓慢的表型,这与非 RP 基因表达减少以及氨基酸掺入率下降有关。受 Stb3 影响的基因与 TGAAAAA 基序有关。Stb3 在静止细胞中仅限于核内,在葡萄糖补充后立即释放到细胞质中。Stb3OE 生长缓慢的表型可以通过 Hos2 组蛋白去乙酰化酶活性的丧失来逆转,这与抑制涉及组蛋白去乙酰化的观点一致。SCH9 过表达或 PPH22 缺失,这些突变激活了雷帕霉素(Tor)营养感应途径的靶标,也可以逆转 Stb3OE 表型。Tor 信号的抑制会使表型更加严重,并将 Stb3 限制在核内。结果支持这样一种模型,即 Stb3 是在营养物质耗尽时抑制一大组生长基因的组件之一。这种抑制作用被葡萄糖所终止。