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

存储在遗传物质（DNA）基因序列中的关键信息必须由细胞解码，以便在需要时产生各种各样的必需蛋白质。每个基因的序列指定了给定蛋白质的序列，而许多蛋白质本身又负责细胞中其他类型结构的合成。从DNA到蛋白质的一般信息传递是由信使RNA （mRNA）完成的，信使RNA是DNA序列的副本，必须通过称为核糖体的高度调节的复杂机器进行解码，这一过程称为翻译。为了高效、准确地工作，并使核糖体在细胞的最佳利益中发挥作用，这一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，eIF4G，作为一个支架蛋白，核糖体和其他几个起始因子聚集在其上。在哺乳动物细胞中，两个略有不同的基因包含eIF4G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eIF4G蛋白是否在细胞中执行不同或重叠的功能。利用一个模型细胞系统概括了在体内发挥作用的控制系统，我们希望研究这些翻译机制组件的组装在选择特定mrna进行翻译中的作用，从而使细胞能够制造肌肉细胞再生所需的正确类型和数量的蛋白质。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失调的mrna的特异性控制。

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.