Unr - master regulator of mRNA translation

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All cells in our body need to be able to turn genes on and off at the right times; it is important to know how this is controlled, in order to understand processes such as development and aging. Many genes function together in the same processes within a cell, so need to be turned on, or expressed, together. To achieve this, there are some proteins that control many genes at once - master regulators. One protein that we believe acts in this way is called Unr. Mice that do not have Unr are not viable - the embryos die during development - which shows that this protein is crucial for the functioning of a healthy animal. Our preliminary studies have shown that Unr can stimulate the expression of many, but not all, genes. Although we know that Unr is very important, and we know that it has a role in gene expression, we do not know: 1) which genes Unr turns on, or 2) how it does this. The objectives of this project are to find answers to these two questions. Firstly, we will use an antibody that recognises Unr to isolate the protein from human cells, along with all the different genes that it is interacting with. We will then be able to identify those genes, and the specific parts of those genes that mark them out to be turned on by Unr. We will also compare healthy cells with cells that do not have Unr, and look to see which genes are no longer expressed in the absence of Unr. Secondly, we will carry out experiments to test which other proteins Unr interacts with in order to stimulate expression of a gene. We already know some of the proteins that Unr interacts with, but not whether these interactions are important for its function in gene expression, or how these interactions enable Unr to turn a gene on. In unravelling the function of the master regulator Unr, this project will increase knowledge of the complicated regulation of gene expression in human cells, and help to shed light on how the human body develops and ages.