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.

储存在遗传物质（DNA）的基因序列中的关键信息必须由细胞解码，以产生各种必需的蛋白质。每个基因的序列指定了给定蛋白质的序列，许多蛋白质本身又负责细胞中其他类型结构的合成。信息从DNA到蛋白质的一般转移是由信使RNA（mRNA）完成的，信使RNA是DNA序列的拷贝，必须由一个复杂的、高度调节的机器（称为核糖体）解码，这一过程称为翻译。为了有效、准确地工作，并使核糖体以细胞的最佳利益发挥作用，这种机制需要其他蛋白质（翻译起始因子; eIF）以高度调节的方式相互作用，mRNA和核糖体。其中之一，eIF 4G，作为一个支架蛋白，核糖体和其他几个起始因子组装。在哺乳动物细胞中，两个略有不同的基因含有eIF 4G的序列，这两个基因也表达最终蛋白的不同变体。然而，目前我们还不知道这些不同形式的eIF 4G蛋白在细胞中是否具有不同或重叠的功能。使用一个模型细胞系统，概括控制系统显示在体内发挥作用，我们希望调查的作用，选择特定的mRNA翻译，使细胞，使正确的类型和数量的蛋白质所需的肌肉细胞再生的翻译机制的这些组件的组装。这项研究将提高我们对基因表达不同阶段的理解，也可能导致对疾病期间失调的某些mRNA的特异性控制。