Whi3, an S. cerevisiae RNA-Binding Protein, Is a Component of Stress Granules That Regulates Levels of Its Target mRNAs
Whi3, an S. cerevisiae RNA-Binding Protein, Is a Component of Stress Granules That Regulates Levels of Its Target mRNAs
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DOI：
10.1371/journal.pone.0084060
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发表时间：
2013-12-27
期刊：
影响因子：
3.7
通讯作者：
Cyert, Martha S.
中科院分区：
文献类型：
--
作者：
Holmes, Kristen J.;Klass, Daniel M.;Cyert, Martha S.
RNA结合蛋白（rbp）对mRNA转录物的调控至关重要，可以改变mRNA的定位、降解、翻译和储存。wh3最初是在筛选小细胞大小的突变体中发现的，并且已经被定性为RBP。wh3相互作用mrna参与介导细胞应激反应的鉴定表明，wh3可能参与应激反应性RNA加工。我们发现，当葡萄糖剥夺或热休克时，wh3定位于应激颗粒。wh3在温度范围内的定位动力学和模式与RNA加工颗粒的已知组分有细微但明显的不同。无论是否存在热休克，wh3的缺失都会导致wh3靶rna的相对丰度增加。cln3mrna水平的升高可能解释了Delta细胞细胞大小的减小。wh3的另一个mRNA靶点编码锌响应转录因子Zap1，表明wh3在锌胁迫响应中发挥作用。事实上，我们发现wh3 δ细胞对锌毒性具有增强的敏感性。总之，我们的研究结果提出了一个扩展的wh3功能模型：除了作为细胞周期的调节剂，wh3可能在应激依赖性RNA加工和对各种应激条件的反应中发挥作用。
RNA binding proteins (RBPs) are vital to the regulation of mRNA transcripts, and can alter mRNA localization, degradation, translation, and storage. Whi3 was originally identified in a screen for small cell size mutants, and has since been characterized as an RBP. The identification of Whi3-interacting mRNAs involved in mediating cellular responses to stress suggested that Whi3 might be involved in stress-responsive RNA processing. We show that Whi3 localizes to stress granules in response to glucose deprivation or heat shock. The kinetics and pattern of Whi3 localization in response to a range of temperatures were subtly but distinctly different from those of known components of RNA processing granules. Deletion of Whi3 resulted in an increase in the relative abundance of Whi3 target RNAs, either in the presence or absence of heat shock. Increased levels of the CLN3 mRNA in whi3 Delta cells may explain their decreased cell size. Another mRNA target of Whi3 encodes the zinc-responsive transcription factor Zap1, suggesting a role for Whi3 in response to zinc stress. Indeed, we found that whi3 Delta cells have enhanced sensitivity to zinc toxicity. Together our results suggest an expanded model for Whi3 function: in addition to its role as a regulator of the cell cycle, Whi3 may have a role in stress-dependent RNA processing and responses to a variety of stress conditions.