Role of auxiliary factors in eukaryotic ribosome biogenesis

核糖体是所有生物体内合成蛋白质的细胞器。这些“机器”由少量RNA分子和多种蛋白质组成。核糖体的关键成分是核糖体rna (RNAs)，因为它们直接参与蛋白质合成的不同步骤。核糖体的生物发生是一个重要的细胞过程，是细胞生长和增殖的先决条件。在真核生物中，这个过程发生在核仁中，核仁是细胞核的一个突出的隔室。大多数核仁因子实际上在导致成熟rna产生的复杂途径的各个步骤中起作用。我的实验室对导致成熟rnas产生的细胞和分子事件感兴趣。更具体地说，我们专注于从前体rRNA分子中去除额外序列的裂解反应。我们的目标是确定与小核仁核糖核蛋白相互作用的辅助因子的作用，这是切割反应所必需的。我们将以酵母为模型系统，利用其良好的遗传、生化和分子生物学工具。我们目前正在研究Dbp4和其他两个显然有助于Dbp4发挥其功能的因素。Dbp4是一种公认的RNA解旋酶，可作为分子马达在裂解过程中重新排列RNA-RNA或RNA-蛋白相互作用。重要的是，Dbp4及其相关因子在进化中是保守的，它们是生长所必需的，表明它们执行关键的细胞功能。这些蛋白的人类同源物参与胚胎发育和癌症（Dbp4的同源物DDX10最近被确定为一种“癌症基因”）。了解这三种蛋白质的功能将有助于阐明关键细胞过程的分子机制，并可能为人类疾病的治疗开辟新的途径。

Ribosomes are the organelles that synthesize proteins in all living organisms. These "machines" are constituted of few RNA molecules and multiple proteins. The key components of ribosomes are the ribosomal RNAs (rRNAs) as they are directly involved in the different steps of 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 actually function at various steps of the intricate pathway that leads to the production of mature rRNAs.     My laboratory is interested in the cellular and molecular events that lead to the production of mature rRNAs. More specifically, we focus on the cleavage reactions that remove extra sequences from precursor rRNA molecules. Our objective is to define the role of auxiliary factors that interact with small nucleolar ribonucleoproteins, which are essential for the cleavage reactions.     We will use the yeast Saccharomyces cerevisiae as a model system to take advantage of its well-characterized genetic, biochemical and molecular biology tools. We currently work on Dbp4 and two other factors that apparently help Dbp4 in its function. Dbp4 is a putative RNA helicase that could act as a molecular motor to rearrange RNA-RNA or RNA-protein interactions during the cleavage steps. Importantly, Dbp4 and its associated factors are conserved in evolution and they are essential for growth, indicating that they perform crucial cellular functions. Human homologues of these proteins are involved in embryonic development and cancer (the homologue of Dbp4, DDX10, has recently been identified as a "cancer gene"). Understanding how these three proteins function will contribute to the elucidation of molecular mechanisms underlying critical cellular processes and could open new avenues for the treatment of human diseases.