Exploring the hidden small proteome of a unicellular eukaryote

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，这种信息不能直接读取：它首先需要被复制到另一种称为信使RNA(信使RNA)的分子中，它可以从信使RNA‘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。细胞还产生其他不能被翻译成蛋白质的RNA(非编码RNA，或ncRNAs)，这些蛋白质在细胞中扮演着其他角色。蛋白质的特性可以从RNA的序列中预测出来。此外，还可以使用专门的技术直接识别蛋白质。然而，这两种方法在识别非常小的蛋白质方面都非常低效。因此，这些蛋白质在很大程度上被研究人员忽视了，尽管有一些小蛋白质具有关键的生物学功能。最近开发了一种新的实验方法，可以检测细胞中活跃翻译的每个RNA区域。根据这些数据，可以预测所有的蛋白质，而不考虑它们的大小。这种方法是以核糖体的名字命名的，核糖体是执行翻译的细胞机器。将这种方法应用于几个生物体，已经揭示了数百个以前未知的预测短蛋白的存在。这些翻译区域中的许多存在于被认为没有翻译的RNA(NcRNAs)中。在一些生物体中，这些短MY蛋白占所有已知蛋白的20%。我们的目标是系统地识别小蛋白并了解它们是如何工作的。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。为了研究这些问题，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。我们将使用不同的方法来鉴定这些细胞产生的所有小蛋白。然后，我们将去除单个蛋白质，并研究这如何影响细胞的生长和繁殖。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 messenger RNA (mRNA), from which it can be 'translated' into a protein. Proteins are the components that directly build the cell and make it function. Cells also produce other RNAs that are not translated to make proteins (non-coding RNAs, or ncRNAs), which have other roles in the cell.The identity of a protein can be predicted from the sequence of the RNA. Moreover, proteins can also be identified directly using specialized techniques. However, both approaches are very inefficient at identifying very small proteins. Thus, these proteins have been largely ignored by researchers, even though there are examples of small proteins with key biological functions.A new experimental method has been recently developed that allows the detection of every RNA region that is actively translated in a cell. From these data, all proteins can be predicted regardless of their size. The method is called 'ribosome-profiling' after the ribosome, which is the cellular machine that carries out translation. The application of this approach to several organisms has revealed the existence of hundreds of previously unknown predicted short proteins. Many of these translated regions were in RNAs that were not thought to be translated (ncRNAs). In some organisms, these short may proteins represent as much as 20% of all previously known proteins.Our aims are to identify small proteins systematically and to understand how they work. 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 these questions we will use a simple yeast -made of a single cell- that can acquire different forms. We will use different methods to identify all small proteins produced by these cells. We will then remove individual proteins and study how this affects how cells grow and reproduce. We expect this information will be useful to understand how human cells behave and, eventually, help us devise cures for disease.