Proteins in RNA-based Enzymes

RNA 酶中的蛋白质

• 批准号: 8694771
• 负责人: ANDREY S. KRASILNIKOV
• 金额: $ 31.4万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8694771
• 关键词: Bacteria; Binding; Biochemical; Catalysis; Catalytic Domain; Catalytic RNA; Cell physiology; Cells; Complex; Disease; Dwarfism; Elements; Enzymes; Eukaryota; Eukaryotic Cell; Evolution; Family; Funding; Goals; Hair; Human; Immunologic Deficiency Syndromes; In Vitro; Knowledge; Learning; Life; Light; Maps; Modality; Modeling; Mutation; Nucleotides; Play; Process; Proteins; Public Health; RNA; RNA Folding; RNA Processing; RNA Splicing; RNA-Protein Interaction; RNAse MRP; RNase P; Reliance; Ribonucleoproteins; Role; Saccharomyces cerevisiae; Shapes; Specificity; Structure; Substrate Specificity; Testing; Time; Transfer RNA; Translations; Yeasts; base; cartilage development; innovation; insight; novel; protein function; public health relevance; tRNA Precursor

DESCRIPTION (provided by applicant): Project Summary RNA-based enzymes play key roles in a wide range of cellular processes, from RNA processing to splicing to translation. While RNA is their catalytic moiety, cellular RNA-based enzymes are ribonucleoproteins (RNPs). The structural and functional roles of proteins and RNA-protein interactions in RNA-based enzymes and RNPs in general are poorly understood. This proposal focuses on S. cerevisiae Ribonuclease (RNase) P and the closely related RNase MRP as a biologically significant and effective model to understand the roles of proteins and RNA-protein interactions in the structure, function, and evolution of ribonucleoproteins. RNases P/MRP are a family of essential RNA-based enzymes that have their origin in the bacterial RNase P ribozyme. In addition to its catalytic RNA moiety, RNase P has a single protein in bacteria, but nine essential proteins in yeast; the protein content increases from ~10% in bacteria to more than 75% in eukaryotes. The reasons for the increased reliance on proteins in the eukaryotic RNase P are not understood, and the functions of the proteins themselves are not known. RNase MRP is an essential eukaryotic RNP. Yeast RNase MRP has a 340-nucleotide-long catalytic RNA which resembles the RNA component of RNase P and 10 essential protein components, eight of which are shared with RNase P. The structural organization of RNase MRP and the roles of its components are not clear. The large and complex eukaryotic RNase P and, especially, RNase MRP are understudied; this proposal aims to fill the gap in our understanding of these fundamentally important catalytic RNPs, and expand our understanding of RNA- protein interactions in general. The specific aims of the proposal are: (1) Characterize respective contributions of proteins and RNA to specificities of RNase P and RNase MRP RNPs; (2) Determine roles of proteins and RNA-protein interactions in the structural organizations of RNases P/MRP and catalysis. We will characterize the RNA-protein interactions in RNases P/MRP using biochemical studies and structural analysis, and clarify the roles of the proteins in RNases P/MRP.

描述（由申请人提供）： 基于项目摘要的基于RNA的酶在从RNA处理到剪接再到翻译的各种细胞过程中起关键作用。尽管RNA是其催化部分，但基于细胞RNA的酶是核糖核蛋白（RNP）。一般而言，蛋白质和RNA - 蛋白质相互作用的结构和功能作用一般而言。该提案的重点是酿酒酵母核糖酶（RNase）P和密切相关的RNase MRP，作为一种具有生物学意义和有效的模型，以了解蛋白质和RNA蛋白相互作用在结构，功能和核糖核蛋白的进化中的作用。 RNases P/MRP是基于RNA的必需酶家族，它们起源于细菌RNase P核酶。除了其催化RNA部分外，RNase P还具有细菌中的单个蛋白质，但酵母中有9种必需蛋白。蛋白质含量从细菌的约10％增加到真核生物的75％以上。尚不清楚真核RNase P中对蛋白质蛋白质的依赖性增加的原因，并且尚不清楚蛋白质本身的功能。 RNase MRP是必不可少的真核RNP。酵母RNase MRP具有340个核苷酸长的催化RNA，类似于RNase P的RNA成分和10个必需蛋白质成分，其中八个与RNase P共享。RNaseMRP的结构组织及其组件的作用尚不清楚。大而复杂的真核RNase P，尤其是RNase MRP研究了；该建议旨在填补我们对这些根本重要的催化RNP的理解，并扩展我们对RNA蛋白相互作用的理解。该提案的具体目的是：（1）表征蛋白质和RNA对RNase P和RNase MRP RNP的特异性的各自贡献； （2）确定蛋白质和RNA蛋白相互作用在RNases P/MRP和催化的结构组织中的作用。我们将使用生化研究和结构分析来表征RNA酶P/MRP中RNA蛋白的相互作用，并阐明蛋白质在RNases P/MRP中的作用。