Role of RNA-binding proteins in cellular differentiation: a global approach

我们的身体由非常不同类型的细胞组成：皮肤细胞是扁平的，保护我们的身体，而脑细胞有传递信息的电缆。尽管差异如此之大，但我们所有的细胞在它们的基因中携带着完全相同的信息。它们的特别之处在于它们使用了什么信息，也就是说，它们开启和关闭了哪些基因。当细胞使用错误的基因时，许多疾病--如癌症--就会出现。有关如何制造细胞的信息以DNA分子的形式存储。然而，这种信息不能被直接读取：它首先需要被复制到另一种名为RNA的分子中，它可以从RNA中被翻译出来？变成一种蛋白质。蛋白质是直接构建细胞并使其发挥功能的组件。从细胞中制造RNA分子的那一刻起，不同的蛋白质就附着在细胞上，指导着细胞生命的每一步。这些蛋白质被称为RNA结合蛋白，它们对RNA进行修饰，使其能够被翻译成蛋白质，决定它何时应该被破坏，或者它应该被运输到细胞的哪个部位。RNA结合蛋白很重要，因为它们调节DNA和蛋白质之间的信息流。当RNA结合蛋白不能正常发挥作用时，细胞就会失去对许多蛋白质生产的控制，这可能会导致疾病。例如，某些RNA结合蛋白的缺陷会导致肌肉萎缩或智力迟缓等后果。我的目的是了解RNA结合蛋白是如何控制RNA分子的命运的。研究人体复杂过程的一种方法是使用模型生物体：这是一种更简单的生物，但足够相似，可以让我们了解自己。为了研究RNA结合蛋白是如何工作的，我将使用一种简单的酵母--由单个细胞组成--它可以获得不同的形式。我将移除RNA结合蛋白，看看这将如何改变细胞使用哪些基因，我还将研究哪些RNA与不同的RNA结合蛋白结合。这将使我了解细胞如何控制它们的基因以变得不同。我希望这些信息将有助于了解人类细胞的行为，并最终帮助我们设计出治疗疾病的方法。

Our bodies are made of very different types of cells: Skin cells are flat and protect our body, while brain cells have cables that pass messages around. Despite being so different, all our cells carry exactly the same information in their genes. What makes them special is what information they use, that is, which genes they switch on and off. Many diseases -such as cancer- appear when cells use the wrong genes.The information on how to make a cell is stored in the form of a DNA molecule. However, this information cannot be read directly: it first needs to be copied into another molecule called RNA, from which it can be ?translated? into a protein. Proteins are the components that directly build the cell and make it function.From the moment an RNA molecule is made in the cell different proteins attach to it, directing every step of its life. These proteins, called RNA-binding proteins, modify the RNA so that it can be translated into a protein, decide when it should be destroyed or to which part of the cell it should be transported.RNA-binding proteins are important because they regulate the flow of information between DNA and proteins. When RNA-binding proteins do not function correctly, the cell loses control on the production of many proteins, and this may cause disease. For instance, defects in certain RNA-binding proteins lead to consequences such as muscular dystrophy or mental retardation.My aim is to understand how RNA-binding proteins control the fate of RNA molecules. One way to study a complicated process of the human body is to use a model organism: this is a simpler creature, but similar enough to allow us to learn about ourselves. To study how RNA-binding proteins work I will use a simple yeast -made of a single cell- that can acquire different forms. I will remove RNA-binding proteins and see how this changes which genes are used by the cell, and I will study which RNAs are bound by different RNA-binding proteins. This will allow me to understand how cells control their genes in order to become different. I expect this information will be useful to understand how human cells behave and, eventually help us devise cures for disease.