Role of RNA-binding proteins in the control of RNA turnover: a genome-wide 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。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，从那里它可以被‘翻译’成一种蛋白质。蛋白质是直接构建细胞并使其发挥功能的成分。细胞中每个RNA分子的数量必须仔细控制。例如，当细胞含有错误数量的特定RNA时，许多疾病--如癌症--就会出现。所有RNA的水平是由它们产生的速度和被破坏的速度之间的平衡来确定的。虽然这两个方面同样重要，但我们对细胞如何控制RNA的破坏知之甚少。从RNA分子形成的那一刻起，不同的蛋白质就附着在它上面。这些蛋白质被称为RNA结合蛋白，决定了RNA应该在什么时候被破坏。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营养不良或智力迟缓等后果。我们的目标是了解RNA结合蛋白是如何控制RNA分子的破坏的。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结合蛋白的工作原理，我们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。我们将移除RNA结合蛋白，以了解这如何改变RNA被破坏的方式，我们还将研究哪些RNA与不同的RNA结合蛋白结合。这将使我们了解细胞如何控制它们的基因以变得不同。我们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.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.The amount of each RNA molecule in a cell has to be carefully controlled. For example, many diseases -such as cancer- appear when cells contain the wrong amounts of certain RNAs. The levels of all RNAs are set by the balance between how quickly they are made and how fast they are destroyed. Although both aspects are equally important, we know much less about how cells control the destruction of RNAs.From the moment an RNA molecule is made, different proteins attach to it. These proteins, called RNA-binding proteins, decide when the RNA should be destroyed. When RNA-binding proteins do not function correctly, the cell loses control of 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.Our aim is to understand how RNA-binding proteins control the destruction 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 we will use a simple yeast -made of a single cell- that can acquire different forms. We will remove RNA-binding proteins to see how this changes the way in which RNAs are destroyed, and we will study which RNAs are bound by different RNA-binding proteins. This will allow us to understand how cells control their genes in order to become different. We expect this information will be useful to understand how human cells behave and, eventually, help us devise cures for disease.