Center for Genomic Information Encoded by RNA Nucleotide Modifications

摘要：转录后机制控制着几乎每个细胞中的基因表达。一位少校 转录后基因调控的中介是翻译核糖体，它由三个不同的核糖体组成。 RNAs的类型：rRNA、tRNA和mRNA。这些RNA与核糖体和mRNA结合蛋白一起形成 一种多核糖核酸/多蛋白复合体，可显著影响信使核糖核酸的稳定性和翻译。重要的是 这种情结不是结构性的。相反，rRNA-tRNA、rRNA-mRNA和tRNA-mRNA的相互作用是高度相互作用的 尽管人们对其调控机制知之甚少。潜在的机制可以 包括对它们的核苷酸进行化学修饰。事实上，rrna、trna和mrna受到不同的 化学修饰，其化学计量比在不同的组织或疾病状态下受到高度调控。我们的 潜在的假设是rrna、trna和mrna中受调控的核苷酸修饰起到了“密码”的作用。 它控制这些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的核苷酸修饰可能是基因的关键调节因子。 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量化和分析核苷酸 RRNA、tRNA和mRNA的修饰。另一个问题是理解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都有专门的专业知识。它是 因此，对于rRNA、tRNA和mrna的专家来说，共同努力破译rRNA、tRNA和mRNA的相互作用至关重要。 这些RNA。该中心将汇集这些不同类型的RNA方面的专家团队，他们将工作 共同开发新的技术来探测核苷酸修饰以及它们如何相互作用来协调 独特的基因表达模式。该中心将开发新的测绘和量化技术 RRNA、tRNA和mRNA修饰，识别组织和疾病中的动态修饰位置，以及 确定这些动态修改的功能。中将开发的方法和数据集 该中心将提供加速新的表位转录组学领域所需的基础知识 RRNA、tRNA和信使核糖核酸生物学研究。该中心肩负着重要的外展和教育使命。这个 外展/教育机会将包括赞助的本科生研究、突破性项目资助、 为代表性不足的少数族裔受训人员提供项目资金，为培训访问外部调查人员提供资金，以及 为年度研讨会提供资金。我们还将开发一个网站来管理表位转录图谱 中心生成的数据，以确保快速、轻松地访问我们生成的新数据。总体而言， 该中心的使命是作为培训表位转录组学研究人员的中心，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，这是开辟表位转录组学研究的新领域所必需的。

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.