Molecular mechanisms connecting signal transduction and RNA processing: Structural studies of the STAR family of protein

转录后基因调控是细胞中的一个主要调控事件，它允许有限数量的基因产生蛋白质多样性。这些调节是由细胞外信号通过细胞信号来调节的。我们对控制这些调控和调节的分子机制知之甚少。我打算在分子水平上研究一个叫做STAR的蛋白质家族，它连接细胞信号传导和转录后基因调控。为此，我将使用生物化学和生物物理方法的结合，特别是核磁共振波谱。该项目的第一个主要方面将是描述STAR蛋白如何特异性识别其靶rna的结构特征。第二个方面将涉及蛋白质-蛋白质相互作用，并将表征细胞信号传导如何影响这些蛋白质在转录后基因调控中的功能。由于这些蛋白质在肿瘤进展和逆转录病毒（如HIV-1）的生命周期中发挥作用，因此这些结构研究将为开发针对癌症和逆转录病毒治疗的特异性药物提供分子基础。

Post-transcriptional gene regulation is a major regulatory event in cells that allow for protein diversity out of a limited number of genes. These regulations are modulated by extracellular signals through cell signalling. Very little is known about the molecular mechanisms that govern these regulations and modulations. I intend to study at a molecular level a family of proteins, called STAR, which connects cell signalling and post-transcriptional gene regulation. For that I will use a combination of biochemical and biophysical methods, especially NMR spectroscopy. The first main aspect of the project will be to characterize structurally how STAR proteins specifically recognize their target RNAs. The second aspect will involve protein-protein interactions and will be to characterize how cell signalling affects the functions of these proteins in post-transcriptional gene regulation.Since these proteins play a role in tumour progression and in the life cycle of retroviruses, like HIV-1, these structural studies will provide the molecular basis for developing specific drugs optimized for cancer and retroviral therapies.