Ribosome biogenesis and nucleolar function

核糖体生物发生和核仁功能

• 批准号: RGPIN-2019-07257
• 负责人: Dragon, François
• 金额: $ 2.62万
• 依托单位: Université du Québec à Montréal
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=739384
• 关键词: Ribosome; biogenesis; nucleolar; function

Ribosomes are the organelles that synthesize proteins in all living organisms. They are formed by the association of two subunits, and each is constituted of large RNA molecules and multiple proteins. The key components of ribosomes are the ribosomal RNAs (rRNAs), which are directly involved in the different steps of protein synthesis. In fact, most antibiotics target rRNAs to perturb protein synthesis. The biogenesis of ribosomes is a major cellular process, and it is a prerequisite for cells to grow in size and proliferate. In eukaryotes, this process takes place in the nucleolus, a prominent compartment of the cell nucleus. The majority of nucleolar factors function at various steps of the intricate pathway that leads to the production of ribosomes. But the nucleolus is not merely a ribosome factory: many other cellular processes are connected to the nucleolus, such as viral replication, aging and cell cycle control. My research program focuses on ribosome biogenesis and nucleolar function. For these studies we use the baker's yeast Saccharomyces cerevisiae because it is the best studied model system in the field. Indeed, yeast is a simple eukaryote and we can take advantage of its well-characterized genetics, in combination with powerful biochemical and molecular biology tools. One of the major tasks of my laboratory is to understand the early events of ribosome formation, and to decipher the molecular mechanisms involving nucleolar factors that participate in the production of mature rRNAs. For the next five years we will work on highly conserved nucleolar factors: the RNA helicase Dbp4, the RNA acetyltransferase Kre33, and ribosomal protein S18, all of which are necessary to form the small ribosomal subunit. We have also initiated studies on two nucleolar RNA methyltransferases that we call Nop38 and Nop36; these enzymes are highly conserved, yet their target(s) are not known, but we have indications they could have a role in ribosome biogenesis. Our research on these nucleolar factors is important to understand how they function in the cell: elucidation of molecular mechanisms underlying ribosome biogenesis in eukaryotes could open new avenues to improve the growth of cells or target eukaryotic pathogens that affect plants and other animals.

核糖体是所有生物体中合成蛋白质的细胞器。它们是由两个亚基结合而成，每个亚基由大RNA分子和多种蛋白质组成。核糖体的关键成分是核糖体RNA（rRNA），它直接参与蛋白质合成的不同步骤。事实上，大多数抗生素靶向rRNA以干扰蛋白质合成。核糖体的生物发生是一个主要的细胞过程，是细胞生长和增殖的先决条件。在真核生物中，这一过程发生在核仁中，核仁是细胞核的一个突出部分。大多数核仁因子在导致核糖体产生的复杂途径的各个步骤中发挥作用。但核仁不仅仅是一个核糖体工厂：许多其他细胞过程都与核仁有关，如病毒复制，衰老和细胞周期控制。我的研究项目主要集中在核糖体生物发生和核仁功能。对于这些研究，我们使用面包酵母酿酒酵母，因为它是该领域研究最好的模型系统。事实上，酵母是一种简单的真核生物，我们可以利用其良好的遗传特性，结合强大的生物化学和分子生物学工具。我实验室的主要任务之一是了解核糖体形成的早期事件，并破译参与成熟rRNA产生的核仁因子的分子机制。在接下来的五年里，我们将研究高度保守的核仁因子：RNA解旋酶Dbp 4，RNA乙酰转移酶Kre 33和核糖体蛋白S18，所有这些都是形成核糖体小亚基所必需的。我们还启动了对两种核仁RNA甲基转移酶的研究，我们称之为Nop 38和Nop 36;这些酶高度保守，但它们的靶点尚不清楚，但我们有迹象表明它们可能在核糖体生物合成中发挥作用。我们对这些核仁因子的研究对于了解它们在细胞中的功能非常重要：阐明真核生物中核糖体生物发生的分子机制可以为改善细胞生长或靶向影响植物和其他动物的真核病原体开辟新途径。