Structure, function and evolution of small RNAs in unicellular eukaryotes

小的核糖核酸(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各种生物中的基因表达。我们直到最近才意识到这些分子在一些真核生物中的绝对多样性和数量。这是一个值得注意的发现，人类基因组的大部分实际上可能包含编码小RNA分子的序列，而不是蛋白质。然而，在大多数生物中，我们仍然不知道这些RNA的身份或细胞内功能。我的研究计划的一个主要目标将是表征新的RNA分子，并阐明它们特定的细胞活动。我们还将研究这些小RNA通过编码它们的基因表达的方式。细胞中的小RNA与蛋白质分子结合形成核糖核蛋白(RNP)复合体。一些特征最好的RNP复合体也是已知的一些最古老的生物结构，它们的存在早于几十亿年前细菌和真核生物的分化。真核生物中的一类RNPs被称为小核仁(Sno)RNPs。这些复合体在真核生物和古生物中都有发现，它们在核糖体的合成和功能中发挥着重要的作用。最近的发现还表明，这些RNPs还有其他不同和重要的细胞功能。我研究的另一个重要目标是确定这些snoRNP复合体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体中的结构和功能来研究这些复合体的进化。为了实现这一目标，我选择在被称为原生生物的单细胞真核生物组中研究这些复合体。在这些研究中，我们不仅将努力加强我们对蛋白质-RNA复合体的结构和功能的了解，而且还将获得操纵这些结构以在诸如人类等生物体中执行新的和有用的功能所需的知识。

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.