Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, IL 60208, USA.
Curr Biol. 2009 Dec 29;19(24):2114-20. doi: 10.1016/j.cub.2009.10.071. Epub 2009 Dec 3.
Spatial control of gene expression, at the level of both transcription and translation, is critical for cellular differentiation [1-4]. In budding yeast, the conserved Ndr/warts kinase Cbk1 localizes to the new daughter cell, where it acts as a cell fate determinant. Cbk1 both induces a daughter-specific transcriptional program and promotes morphogenesis in a less well-defined role [5-8]. Cbk1 is essential in cells expressing functional Ssd1, an RNA-binding protein of unknown function [9-11]. We show here that Cbk1 inhibits Ssd1 in vivo. Loss of this regulation dramatically slows bud expansion, leading to highly aberrant cell wall organization at the site of cell growth. Ssd1 associates with specific mRNAs, a significant number of which encode cell wall remodeling proteins. Translation of these messages is rapidly and specifically suppressed when Cbk1 is inhibited; this suppression requires Ssd1. Transcription of several of these Ssd1-associated mRNAs is also regulated by Cbk1, indicating that the kinase controls both the transcription and translation of daughter-specific mRNAs. This work suggests a novel system by which cells coordinate localized expression of genes involved in processes critical for cell growth and division.
基因表达的空间控制,无论是转录还是翻译水平的控制,对于细胞分化都至关重要[1-4]。在 budding yeast 中,保守的 Ndr/warts 激酶 Cbk1 定位于新的子细胞中,在那里它充当细胞命运决定因子。Cbk1 既诱导了特定于子细胞的转录程序,又以一种定义不明确的作用促进了形态发生[5-8]。在表达功能正常的 Ssd1 的细胞中,Cbk1 是必需的,Ssd1 是一种未知功能的 RNA 结合蛋白[9-11]。我们在这里表明,Cbk1 在体内抑制 Ssd1。这种调控的缺失会显著减缓芽的扩张,导致细胞生长部位细胞壁组织高度异常。Ssd1 与特定的 mRNAs 结合,其中许多编码细胞壁重塑蛋白。当 Cbk1 被抑制时,这些消息的翻译会迅速且特异性地受到抑制;这种抑制需要 Ssd1。这些 Ssd1 相关 mRNAs 的几个转录也受到 Cbk1 的调节,表明激酶控制子细胞特异性 mRNAs 的转录和翻译。这项工作提出了一个新的系统,细胞通过该系统协调与细胞生长和分裂关键过程相关的基因的局部表达。