Regulation of mRNA-5'cap-related posttranscriptional gene expression events by Dcs2 a novel modulatory protein

活细胞基因中包含的信息必须转化为细胞成分，形成结构并使生化反应发生。这个过程被称为基因表达，它对所有生命都至关重要。基因表达包括两个主要步骤，称为转录和翻译。在转录过程中，基因DNA序列中的信息在所谓的信使RNA （mRNA）分子中转化为等效序列。在翻译过程中，mRNA分子被一种叫做核糖体的大分子结构“读取”，核糖体利用这些信息来指挥蛋白质的合成。每个细胞都必须合成和分解自己的mRNA分子，因为这种持续的转换使细胞能够更快地调整基因表达模式，以适应特定生长条件下对特定蛋白质需求的变化。这项拨款提案描述了我们如何希望通过研究一种调节RNA代谢中一个组成步骤的蛋白质（称为Dcs2）来更好地理解mRNA的代谢。更具体地说，动物（包括人类）、植物、昆虫和真菌的细胞通过在一个称为帽的结构中添加甲基化的鸟苷碱基来修饰每个mRNA分子的开始（称为5'端）。我们已经发现，研究中的调节蛋白决定了这个帽结构被移除的速度。这种去除帽状结构的过程（“脱帽”）会影响细胞中能够抑制重要细胞过程的RNA衰变中间体的水平。此外，我们有初步证据表明，帽状结构中甲基化G碱基的可用性会影响细胞核酸中积累的错误数量，从而影响细胞衰老的速度。基于这些以及其他原因，我们希望了解新发现的调节蛋白Dcs2的作用模式和功能意义。

The information contained in the genes of living cells has to be converted into cellular components that form structures and enable biochemical reactions to take place. This process is called gene expression and it is vital to all life. Gene expression comprises two main steps, called transcription and translation. In transcription, the information in the DNA sequences of the genes is converted into equivalent sequences in so-called messenger RNA (mRNA) molecules. In translation, the mRNA molecules are 'read' by a large molecular structure called the ribosome, which uses the information to dictate the synthesis of proteins. Each cell has to synthesize and break down its mRNA molecules, because this continuous turnover allows the cell to adapt its patterns of gene expression more rapidly to changes in the demand for particular proteins which are needed under certain growth conditions. This grant proposal describes how we wish to understand this metabolism of mRNA better by studying a protein (called Dcs2) that regulates a component step in the metabolism of RNA. More specifically, cells of animals (including man), plants, insects and fungi modify the beginning (called the 5'end) of each mRNA molecule by adding a methylated guanosine base in a structure called the cap. We have discovered that the regulatory protein under study determines how rapidly this cap structure is removed. This process of removing the cap structure ('decapping') affects the levels of RNA decay intermediates in the cell that are capable of inhibiting important cellular processes. Moreover, we have preliminary evidence that the availability of the methylated G base found in the cap structure influences the number of errors accumulating in cellular nucleic acids, and thereby the rate of cellular ageing. For these, and other, reasons, we wish to understand the mode of action and functional significance of the newly discovered regulatory protein Dcs2.