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: 10306976
• 负责人: SAMIE R JAFFREY
• 金额: $ 301.59万
• 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/10306976
• 关键词: Address; Affect; Area; Atlases; Biological Assay; Biology; Cell physiology; Cells; Chemicals; Code; Communities; Complex; Coupled; Cryoelectron Microscopy; Data; Data Set; Disease; Ensure; Foundations; Funding; Gene Expression; Gene Expression Profile; Gene Expression Regulation; Genetic Transcription; Genomics; Goals; Knowledge; Maps; Mass Spectrum Analysis; Mediator of activation protein; 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-Binding Proteins; Regulation; Regulator Genes; Research; Research Personnel; Research Project Grants; Ribose; Ribosomal RNA; Ribosomes; Role; Signal Transduction; Site; Structure; Techniques; Technology; Time; Tissues; Training; Transfer RNA; Translating; Translations; Underrepresented Minority; Visit; Work; base; cell type; epitranscriptome; epitranscriptomics; human tissue; insight; minority trainee; new technology; novel; online resource; outreach; 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.

转录后机制控制几乎每个细胞中的基因表达。一个主要 转录后基因调控的介质是翻译核糖体，其包括三种不同的核糖体。 RNA的类型：rRNA、tRNA和mRNA。这些RNA，沿着核糖体和mRNA结合蛋白， 一种多RNA/多蛋白复合物，可显著影响mRNA的稳定性和翻译。重要的是， 该复合物不是组成性的。相反，rRNA-tRNA，rRNA-mRNA和tRNA-mRNA相互作用是高度相关的。 尽管对其调控机制知之甚少，一种潜在的机制可以 涉及它们核苷酸的化学修饰。事实上，rRNA、tRNA和mRNA受到不同的 化学计量在不同组织或疾病状态中高度调节的化学修饰。我们 基本假设是rRNA、tRNA和mRNA中受调控的核苷酸修饰充当“密码”， 控制这些RNA及其相互作用，从而编码独特的基因表达模式。 尽管rRNA、tRNA和mRNA核苷酸修饰有望成为基因表达的关键调节因子， 表达，研究这些修饰如何相互影响以控制基因表达， 很难探索。这在一定程度上反映了缺乏可扩展的方法来定量和分析核苷酸 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一个领域的专业知识。是 因此，rRNA、tRNA和mRNA的专家们必须共同努力，破译 这些RNA。该中心将汇集一个在这些不同类型的RNA的专家团队， 共同开发新技术来探测核苷酸修饰以及它们如何相互作用以协调 独特的基因表达模式该中心将开发新的技术， rRNA、tRNA和mRNA修饰，鉴定组织和疾病中的动态修饰位点， 确定这些动态修改的功能。将开发的方法和数据集 该中心将提供加速发展表观转录组学新领域所需的基础知识 rRNA、tRNA和mRNA生物学研究。该中心有一个主要的外展和教育使命。的 推广/教育机会将包括赞助的本科生研究，突破项目资金， 为代表性不足的少数族裔受训人员提供项目资金，为培训外部访问调查人员提供资金， 为年度研讨会提供资金。我们还将开发一个网站， 数据中心生成的数据，以确保快速，方便地访问我们生成的新数据。总体看 中心的使命是作为一个中心，培训研究人员在epitranscriptomics，以及开发新的 使能技术，开发基础数据集，并揭示修饰核苷酸的基本原理 在rRNA、tRNA和mRNA中发挥作用，这是开辟表观转录组学研究新领域所必需的。