The role of initiation factor complex assembly and phosphorylation in controlling mRNA recruitment to ribosomes during differentiation.

起始因子复合物组装和磷酸化在分化过程中控制 mRNA 募集到核糖体中的作用。

• 批准号: BB/E014399/1
• 负责人: Simon Morley
• 金额: $ 36.93万
• 依托单位: University of Sussex
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FE014399%2F1
• 关键词: role; initiation; factor; complex; assembly

Critical information stored in the gene sequences of the genetic material (DNA) has to be decoded by the cell to produce a wide variety of essential proteins, as and when they are required. The sequence of each gene specifies the sequence of a given protein, with many proteins themselves in turn responsible for the synthesis of other types of structures in the cell. The general transfer of information from DNA to protein is carried out by the messenger RNA (mRNA), which is a copy of the DNA sequence and has to be decoded by a complex, highly regulated machine termed a ribosome, in a process known as translation. To work efficiently, accurately, and to allow the ribosome to function in the best interests of the cell, this machinery requires other proteins (translation initiation factors; eIF) that interact with each other, the mRNA and the ribosome in a highly regulated manner. One of these, eIF4G, acts as a scaffold protein, onto which the ribosome and several other initiation factors assemble. In mammalian cells, two slightly different genes contain the sequence for eIF4G, and the two genes also express different variants of the final protein. However, at this time we do not know whether these different forms of eIF4G protein perform different or overlapping functions in the cell. Using a model cell system that recapitulates control systems shown to function in the body, we wish to investigate the role of assembly of these components of the translational machinery in selecting specific mRNAs for translation to allow cells to make the correct types and amounts of proteins required for muscle cell regeneration. This study will improve our understanding of the different stages of gene expression, and may also lead to the specific control of certain mRNAs that are deregulated during diseases.

在需要时，必须将存储在遗传材料（DNA）基因序列（DNA）的基因序列（DNA）的基因序列中，以产生各种必需蛋白质。每个基因的序列指定给定蛋白的序列，许多蛋白质本身又负责细胞中其他类型的结构的合成。信息从DNA到蛋白质的一般传递是由Messenger RNA（mRNA）进行的，它是DNA序列的副本，必须由一个称为核糖体的复杂的，高度调节的机器解码，在称为翻译的过程中。为了有效，准确地工作并允许核糖体在细胞的最大利益中发挥作用，该机械需要其他蛋白质（翻译起始因子； EIF）相互相互作用，以高度调节的方式，mRNA和核糖体。其中之一是EIF4G充当支架蛋白，核糖体和其他几个起始因子都组装出来。在哺乳动物细胞中，两个略有不同的基因包含EIF4G的序列，两个基因也表达了最终蛋白质的不同变体。但是，目前我们不知道这些不同形式的EIF4G蛋白在细胞中执行不同或重叠的功能。使用模型单元系统概括显示在人体中起作用的控制系统，我们希望研究转化机械组件的组装在选择特定mRNA以进行翻译中的作用，以允许细胞制造正确的蛋白质类型和量用于肌肉细胞再生。这项研究将提高我们对基因表达不同阶段的理解，也可能导致对某些在疾病期间受管制的mRNA的特定控制。