Center for Genomic Information Encoded by RNA Nucleotide Modifications

RNA核苷酸修饰编码的基因组信息中心

• 批准号: 10666637
• 负责人: SAMIE R JAFFREY
• 金额: $ 205.85万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-14 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10666637
• 关键词: Acceleration; Address; Affect; Area; Biological Assay; Biology; Cell physiology; Cells; Chemicals; Code; Communities; Complex; Coupled; Cryoelectron Microscopy; Data; Data Set; Disease; Education and Outreach; Ensure; Funding; Gene Expression; Gene Expression Profile; Gene Expression Regulation; Genetic Transcription; Genomics; Goals; Knowledge; Maps; Mass Spectrum Analysis; Mediator; Messenger RNA; Methods; Mission; Modification; Molecular Conformation; Multiprotein Complexes; Nucleotides; Pathogenesis; Pattern; Peptide Synthesis; Post-Transcriptional Regulation; Protocols documentation; Pseudouridine; RNA; RNA Caps; RNA Stability; RNA analysis; RNA, Ribosomal, 28S; RNA-Binding Proteins; Regulation; Regulator Genes; Research; Research Personnel; Research Project Grants; Ribose; Ribosomal Interaction; Ribosomal RNA; Ribosomes; Role; Signal Transduction; Site; Structure; Techniques; Technology; Time; Tissue atlas; Tissues; Training; Transfer RNA; Translating; Translations; Underrepresented Minority; Visit; Work; cell type; epitranscriptome; epitranscriptomics; human tissue; insight; minority trainee; new technology; novel; online resource; posttranscriptional; single molecule; single-molecule FRET; stoichiometry; sugar; symposium; tool; transcriptome; transcriptome sequencing; undergraduate research; virtual; web site

SUMMARY: Post-transcriptional mechanisms control gene expression in virtually every cell. A major mediator of post-transcriptional gene regulation is the translating ribosome, which comprises three different types of RNAs: rRNA, tRNA and mRNA. These RNAs, along with ribosomal and mRNA-binding proteins, form a multi-RNA/multi-protein complex that can markedly influence mRNA stability and translation. Importantly, this complex is not constitutive. Instead, rRNA-tRNA, rRNA-mRNA, and tRNA-mRNA interactions are highly regulated, although the mechanisms of its regulation are poorly understood. A potential mechanism may involve chemical modification of their nucleotides. Indeed, rRNA, tRNA and mRNA are subjected to diverse chemical modifications whose stoichiometry is highly regulated in different tissues or disease states. Our underlying hypothesis is that the regulated nucleotide modifications in rRNA, tRNA, and mRNA act as a “code” that controls these RNAs and their mutual interactions, thus encoding unique patterns of gene expression. Although rRNA, tRNA, and mRNA nucleotide modifications are poised to be critical regulators of gene expression, studying how these modifications influence each other to control gene expression has been difficult to explore. In part this reflects the lack of scalable methods to quantify and profile nucleotide modifications in rRNA, tRNA, and mRNA. Another problem is that understanding the interactions of rRNA, tRNA, and mRNA requires specialized expertise in each of these three major areas of RNA biology. It is therefore critical for experts in rRNA, tRNA, and mRNA to work together to decipher the mutual interactions of these RNAs. The Center will bring together a team of experts in these diverse types of RNAs who will work together to develop novel techniques to probe nucleotide modifications and how they interact to orchestrate unique patterns of gene expression. The Center will develop novel technologies for mapping and quantifying rRNA, tRNA, and mRNA modifications, identify the dynamic modification sites in tissues and disease, and determine the function of these dynamic modifications. The methods and datasets that will be developed in the Center will provide the foundational knowledge needed to accelerate new areas of epitranscriptomics research in rRNA, tRNA, and mRNA biology. The Center has a major outreach and educational mission. The outreach/educational opportunities will include sponsored undergraduate research, breakout project funding, project funding for underrepresented minority trainees, funding for training visiting outside investigators, and funding for an annual symposium. We will also develop a website that curates the epitranscriptomic mapping data generated by the Center to ensure rapid and easy access to the new data we generate. Overall, the Center’s mission is to serve as a hub for training researchers in epitranscriptomics, as well as to develop new enabling technologies, develop foundational datasets, and reveal fundamental principles of modified nucleotide function in rRNA, tRNA, and mRNA that are needed to open up new areas of epitranscriptomics research.

摘要：转录后机制几乎控制每个细胞中的基因表达。专业 转录后基因调节的介质是翻译核糖体，其中包括三种不同 RNA的类型：rRNA，tRNA和mRNA。这些RNA以及核糖体和mRNA结合蛋白形成 一种可以显着影响mRNA稳定性和翻译的多-RNA/多蛋白质复合物。重要的是， 这个复合物不是构成的。相反，rRNA-tRNA，rRNA-mRNA和tRNA-mRNA相互作用高度高度 受监管的调节机制知之甚少。潜在的机制可能 涉及化学修饰其核苷酸。实际上，rRNA，tRNA和mRNA受到潜水 化学测定法在不同的组织或疾病状态中受到高度调节的化学修饰。我们的 基本的假设是RRNA，tRNA和mRNA中的核苷酸修饰作为“代码” 控制这些RNA及其相互作用，从而编码基因表达的独特模式。 虽然rRNA，tRNA和mRNA核苷酸修饰被中毒为基因的关键调节剂 表达，研究这些修饰如何相互影响以控制基因表达 难以探索。在某种程度上，这反映了缺乏量化和剖面核苷酸的可扩展方法 RRNA，tRNA和mRNA的修饰。另一个问题是了解rRNA的相互作用， tRNA和mRNA需要在RNA生物学的这三个主要领域中的每个领域中的专业知识。这是 因此，对于rRNA，tRNA和mRNA专家至关重要 这些RNA。该中心将汇聚一组专家，这些人将在这些潜水员类型的RNA中工作 共同开发新的技术来探测核苷酸的修饰以及它们如何与编排相互作用 基因表达的独特模式。该中心将开发用于映射和量化的新技术 rRNA，tRNA和mRNA修饰，确定组织和疾病中的动态修饰位点，以及 确定这些动态修改的功能。将在 该中心将提供加速新的表面分类组学领域所需的基本知识 RRNA，tRNA和mRNA生物学的研究。该中心具有重大的宣传和教育任务。这 外展/教育机会将包括赞助的本科研究，分组项目资金， 用于代表性不足的少数民族培训的项目资金，用于培训访问外部调查员的资金以及 每年研讨会的资金。我们还将开发一个网站，该网站策划了上映映射 中心生成的数据可确保快速轻松访问我们生成的新数据。总体而言， 中心的使命是作为培训表面翻译学研究人员的枢纽，并开发新的 启用技术，开发基础数据集并揭示了修改核苷酸的基本原理 开放新的表演组学研究领域所需的RRNA，tRNA和mRNA的功能。