Structure, function and evolution of small RNAs in unicellular eukaryotes

单细胞真核生物小RNA的结构、功能和进化

• 批准号: 355757-2008
• 负责人: Russell, Anthony
• 金额: $ 2.04万
• 依托单位: University of Lethbridge
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2012
• 资助国家: 加拿大
• 起止时间: 2012-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=498169
• 关键词: Structure; function; evolution; small; RNAs

Small ribonucleic acid (RNA) molecules have many essential and varied intracellular functions that affect the expression of genes in organisms ranging from bacteria to humans. We have only recently become aware of the sheer diversity and number of these molecules in some eukaryotic organisms. It is a remarkable discovery that the majority of the human genome may in fact contain sequences coding for small RNA molecules rather than for proteins. In most organisms, however, we still do not know the identity or the intracellular function of these RNAs. A primary objective of my research program will be to characterize novel RNA molecules and to elucidate their specific cellular activities. We will also be examining the means by which these small RNAs are expressed from the genes that encode them. Small RNAs associate in the cell with protein molecules to form ribonucleoprotein (RNP) complexes. Several of the best-characterized RNP complexes are also some of the most ancient biological structures known and their existence predates the divergence of bacterial and eukaryotic organisms several billion years ago. One such class of eukaryotic RNPs are called the small nucleolar (sno)RNPs. These complexes are found in both eukaryotic and archaeal organisms where they play an important role in the synthesis and function of ribosomes. Recent findings also indicate that these RNPs have other distinct and important cellular functions. Another important goal of my research is to determine the detailed mechanism by which these snoRNP complexes function in the process of ribosome synthesis and assembly. We will also investigate the evolution of these complexes by comparing their structure and function in distantly-related organisms. Towards this goal, I have chosen to examine these complexes in the group of unicellular eukaryotic organisms known as protists. In these studies, we will not only be striving to enhance our understanding of the structure and function of protein-RNA complexes, but also to obtain the knowledge required to manipulate these structures to perform novel and useful functions in organisms such as humans.

小核糖核酸（RNA）分子具有许多基本的和不同的细胞内功能，影响从细菌到人类的生物体中基因的表达。我们直到最近才意识到这些分子在某些真核生物中的绝对多样性和数量。这是一个了不起的发现，人类基因组的大部分实际上可能包含编码小RNA分子而不是蛋白质的序列。然而，在大多数生物体中，我们仍然不知道这些RNA的身份或细胞内功能。我的研究计划的主要目标将是表征新的RNA分子，并阐明其特定的细胞活性。我们还将研究这些小RNA从编码它们的基因中表达的方式。小RNA在细胞中与蛋白质分子结合形成核糖核蛋白（RNP）复合物。几种最具特征的RNP复合物也是一些已知的最古老的生物结构，它们的存在早于几十亿年前细菌和真核生物的分化。一种这样的真核RNP被称为小核仁（sno）RNP。这些复合物存在于真核生物和古生物中，它们在核糖体的合成和功能中发挥重要作用。最近的研究结果还表明，这些RNP具有其他独特而重要的细胞功能。我研究的另一个重要目标是确定这些snoRNP复合物在核糖体合成和组装过程中发挥作用的详细机制。我们还将通过比较它们在远亲生物中的结构和功能来研究这些复合物的进化。为了达到这个目标，我选择在被称为原生生物的单细胞真核生物中研究这些复合物。在这些研究中，我们不仅将努力提高我们对蛋白质-RNA复合物的结构和功能的理解，而且还将获得操纵这些结构所需的知识，以在人类等生物体中执行新的和有用的功能。