Regulation of RNA polymerase II by the deubiquitinase Ubp15

去泛素酶 Ubp15 对 RNA 聚合酶 II 的调节

• 批准号: 435833-2013
• 负责人: Robert, François
• 金额: $ 2.19万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2014
• 资助国家: 加拿大
• 起止时间: 2014-01-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=552902
• 关键词: Regulation; RNA; polymerase; II; deubiquitinase

Gene expression regulation is a complex phenomenon. The very first step in that process consists in generating a messenger molecule (the mRNA), a carbon copy of the gene itself. This is called transcription and it is achieved by a large enzyme called RNA polymerase II. Our laboratory has been studying the molecular mechanisms by which transcription by RNA polymerase II is regulated within cells. Recently, we have performed a series of experiments aiming at identifying proteins that interact with RNA polymerase II in different contexts. This provides important insights since proteins -and RNA polymerase II is no different- fulfill their role by interacting with each other in a very precisely and timely regulated manner. Among the proteins that we found interacting in RNA polymerase II is another enzyme called Upb15. Upb15 is a very poorly characterized protein that belongs to a group of enzymes that remove ubiquitin (a very small protein) that are sometimes attached to various proteins. The addition and removal of ubiquitin is an important mechanism for the regulation of proteins. It can, for example, control their degradation, their localization within the cell, their capacity to interact with other proteins or their enzymatic activity. RNA polymerase II was previously shown to be ubiquitinated (modified by the addition of ubiquitin) but no enzyme was ever found to be responsible for removing ubiquiting from RNA polymerase II. This discovery opens the way to the characterization of the regulation of RNA polymerase II by ubiquitination. Given the central role played by this enzyme in gene expression, this project promises to have broad impact in several fields in molecular biology.

基因表达调控是一个复杂的现象。这个过程的第一步是产生一个信使分子（mRNA），这是基因本身的碳拷贝。这就是所谓的转录，它是由一种叫做RNA聚合酶II的大酶实现的。我们的实验室一直在研究RNA聚合酶II转录在细胞内调节的分子机制。最近，我们已经进行了一系列的实验，旨在确定蛋白质的相互作用与RNA聚合酶II在不同的情况下。这提供了重要的见解，因为蛋白质-和RNA聚合酶II没有什么不同-通过以非常精确和及时的调节方式相互作用来实现它们的作用。在我们发现的与RNA聚合酶II相互作用的蛋白质中，有另一种酶叫Ubb 15。Upb 15是一种非常缺乏特征的蛋白质，属于一组去除泛素（一种非常小的蛋白质）的酶，这些泛素有时附着在各种蛋白质上。泛素的添加和去除是蛋白质调节的重要机制。例如，它可以控制它们的降解，它们在细胞内的定位，它们与其他蛋白质相互作用的能力或它们的酶活性。RNA聚合酶II以前被证明是泛素化的（通过添加泛素修饰），但没有发现任何酶负责从RNA聚合酶II中去除泛素化。这一发现开辟了途径的RNA聚合酶II的泛素化调控的特点。鉴于这种酶在基因表达中发挥的核心作用，该项目有望在分子生物学的几个领域产生广泛的影响。