Role of RNA-binding proteins in the control of RNA turnover: a genome-wide approach

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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.