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RNA的酶在广泛的细胞过程中发挥关键作用，从RNA加工到剪接再到翻译。虽然RNA是它们的催化部分，但基于RNA的细胞酶是核糖核蛋白（RNP）。蛋白质的结构和功能作用以及基于RNA的酶和RNP中的RNA-蛋白质相互作用通常知之甚少。本研究以S.本研究旨在将核糖核酸酶（RNase）P和与之密切相关的RNase MRP作为一种生物学上重要且有效的模型，以了解蛋白质和RNA-蛋白质相互作用在核糖核蛋白的结构、功能和进化中的作用。RNase P/MRP是一个基于RNA的必需酶家族，其起源于细菌RNase P核酶。除了其催化RNA部分，RNase P在细菌中具有单一蛋白质，但在酵母中具有九种必需蛋白质;蛋白质含量从细菌中的约10%增加到真核生物中的75%以上。在真核生物RNase P中增加对蛋白质的依赖的原因尚不清楚，并且蛋白质本身的功能也不清楚。RNase MRP是真核生物必需的RNP。酵母RNase MRP具有340个核苷酸长的催化RNA，其类似于RNase P的RNA组分和10种必需蛋白组分，其中8种与RNase P共享。大而复杂的真核RNase P，特别是RNase MRP，研究不足;该提案旨在填补我们对这些根本重要的催化RNP的理解中的差距，并扩展我们对RNA-蛋白质相互作用的理解。该提案的具体目标是：（1）表征蛋白质和RNA对RNase P和RNase MRP RNP特异性的各自贡献;（2）确定蛋白质和RNA-蛋白质相互作用在RNase P/MRP结构组织和催化中的作用。我们将利用生物化学研究和结构分析来表征RNase P/MRP中的RNA-蛋白质相互作用，并阐明RNase P/MRP中蛋白质的作用。