Unr - master regulator of mRNA translation

我们身体中的所有细胞都需要能够在适当的时间开启和关闭基因；为了理解发育和衰老等过程，了解这是如何控制的是很重要的。在细胞内，许多基因在相同的过程中一起起作用，因此需要一起开启或表达。为了达到这个目的，有一些蛋白质可以同时控制许多基因——主调节器。我们认为有一种蛋白质就是以这种方式起作用的，叫做Unr。没有Unr的老鼠不能存活——胚胎在发育过程中死亡——这表明这种蛋白质对健康动物的功能至关重要。我们的初步研究表明，Unr可以刺激许多基因的表达，但不是全部。虽然我们知道Unr非常重要，我们知道它在基因表达中起作用，但我们不知道：1)Unr启动哪些基因，或者2)它是如何做到这一点的。这个项目的目标就是要找到这两个问题的答案。首先，我们将使用一种能够识别Unr的抗体，从人类细胞中分离出这种蛋白质，以及它与之相互作用的所有不同基因。然后我们将能够识别这些基因，以及这些基因的特定部分，这些部分标志着它们是由Unr启动的。我们还将比较健康细胞和没有Unr的细胞，并观察哪些基因在没有Unr时不再表达。其次，我们将进行实验，测试哪些其他蛋白质与Unr相互作用，以刺激基因的表达。我们已经知道一些与Unr相互作用的蛋白质，但不知道这些相互作用对其在基因表达中的功能是否重要，或者这些相互作用如何使Unr开启基因。通过揭示主调控因子Unr的功能，该项目将增加对人类细胞中基因表达复杂调控的认识，并有助于阐明人体如何发育和衰老。

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.