Exploring the hidden small proteome of a unicellular eukaryote

探索单细胞真核生物隐藏的小蛋白质组

• 批准号: BB/M021483/1
• 负责人: Juan Mata
• 金额: $ 70.25万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FM021483%2F1
• 关键词: Exploring; hidden; small; proteome; unicellular

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.

我们的身体是由非常不同类型的细胞组成的：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。尽管如此不同，我们所有的细胞在它们的基因中携带着完全相同的信息。它们的特殊之处在于它们使用了什么样的信息，也就是说，它们开启和关闭了哪些基因。然而，这些信息不能直接读取：它首先需要被复制到另一种称为信使RNA（mRNA）的分子中，然后才能被“翻译”成蛋白质。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RNA，这些RNA不被翻译成蛋白质（非编码RNA或ncRNA），它们在细胞中有其他作用。蛋白质的身份可以从RNA序列中预测。此外，蛋白质也可以直接使用专门的技术进行鉴定。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所忽视，尽管有一些具有关键生物学功能的小蛋白质的例子。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。从这些数据中，可以预测所有蛋白质，而不管它们的大小。这种方法被称为“核糖体分析”，以核糖体命名，核糖体是执行翻译的细胞机器。这种方法在几种生物中的应用揭示了数百种以前未知的预测短蛋白的存在。这些翻译区中的许多位于被认为不被翻译的RNA（ncRNA）中。在某些生物体中，这些小分子蛋白质占所有已知蛋白质的20%，我们的目标是系统地鉴定小分子蛋白质并了解它们的工作原理。研究人体复杂过程的一种方法是使用模型生物：这是一种简单的生物，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-由单细胞制成-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质。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疾病的治疗方法。

项目成果

Long non-coding RNA repertoire and regulation by nuclear exosome, cytoplasmic exonuclease and RNAi in fission yeast

• DOI: 10.1101/158477
• 发表时间: 2017-07
• 期刊: bioRxiv
• 作者: S. Atkinson;S. Marguerat;Danny A. Bitton;María Rodríguez-López;C. Rallis;J. Lemay;Cristina Cotobal;M. Malecki;J. Mata;F. Bachand;J. Bähler

Long noncoding RNA repertoire and targeting by nuclear exosome, cytoplasmic exonuclease, and RNAi in fission yeast.

• DOI: 10.1261/rna.065524.118
• 发表时间: 2018-09
• 期刊: RNA (New York, N.Y.)
• 作者: Atkinson SR;Marguerat S;Bitton DA;Rodríguez-López M;Rallis C;Lemay JF;Cotobal C;Malecki M;Smialowski P;Mata J;Korber P;Bachand F;Bähler J
• 通讯作者: Bähler J

Effects of cycloheximide on the interpretation of ribosome profiling experiments in Schizosaccharomyces pombe.

• DOI: 10.1038/s41598-017-10650-1
• 发表时间: 2017-09-04
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Duncan CDS;Mata J
• 通讯作者: Mata J

Effects of cycloheximide on the interpretation of ribosome profiling experiments in Schizosaccharomyces pombe

放线菌酮对粟酒裂殖酵母核糖体分析实验解释的影响

• DOI: 10.17863/cam.12311
• 发表时间: 2017
• 作者: Duncan D