Positional Marking of RNA Modifications

RNA 修饰的位置标记

• 批准号: 10484658
• 负责人: Gudrun Stengel
• 金额: $ 25.96万
• 依托单位: ALIDA BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-15 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10484658
• 关键词: Affinity; Alternative Splicing; Antibodies; Bar Codes; Benchmarking; Binding Proteins; Biological; Biological Assay; Biological Sciences; Cells; Chemicals; Chimeric Proteins; Code; Coupling; Cytidine Deaminase; Cytosine; DNA; Deaminase; Deamination; Development; Disease; Disease Progression; Drug Targeting; Drug resistance; Elements; Enzymatic Biochemistry; Enzymes; Exhibits; Foundations; Genetic Code; Genetic Transcription; Goals; Health; Human; Label; Location; Malignant Neoplasms; Measures; Messenger RNA; Methods; Modification; Molecular; Oranges; Pathway interactions; Peptides; Performance; Phase; Phenotype; Play; Point Mutation; Positioning Attribute; Preparation; Process; Proteins; RNA; RNA Degradation; RNA library; RNA metabolism; Reader; Reading; Reporting; Resolution; Ribosomal RNA; Risk; Role; Sampling; Science; Structure; Technology; Transfer RNA; Translating; Translation Initiation; Translations; Uracil; Virus Diseases; Work; analytical method; apoB mRNA editing catalytic subunit; base; base editing; commercialization; covalent bond; drug development; epitranscriptome; epitranscriptomics; experimental study; improved; interest; mRNA sequencing; next generation sequencing; protein expression; stoichiometry; trafficking; transcriptome; tumor progression

Project Summary/Abstract RNA modifications, which constitute the epitranscriptome, play vital roles in seemingly all aspects of RNA metabolism and RNA’s role in the Central Dogma. More than 170 naturally occurring chemical modifications to RNA are known, more than 60 of which are found in human RNA of all types: mRNA, tRNA, rRNA, lncRNA, and the others. These modifications are dynamic; their global quantities change in development and during disease progression. They are installed by writer enzymes, read by reader proteins and removed by eraser enzymes, and they have an intrinsic capacity to alter RNA structure and dynamics. They influence translation initiation and termination, translation fidelity, alternative splicing, trafficking between cellular compartments, and regulate RNA degradation. RNA reader, writer and eraser proteins are promising drug targets of high current interest to pharma. Despite this significance, no currently existing analytical method is capable of locating multiple RNA modifications simultaneously with precise locus information and stoichiometry. The focus of this application is to de-risk a positional marking approach to RNA modification analysis that is capable of multiplexing, approaching single base resolution. This technology will be significant because it will provide the first commercial method for profiling and correlating changes of multiple RNA modification types across the entire transcriptome in a given sample.

项目总结/摘要 RNA修饰是RNA的一个重要组成部分，它在RNA的各个方面都起着重要的作用 代谢和RNA在中心法则中的作用超过170种天然化学修饰， RNA是已知的，其中超过60种存在于所有类型的人RNA中：mRNA、tRNA、rRNA、lncRNA和 其他人这些修饰是动态的;它们的整体数量在发育和疾病期间发生变化 进展它们由写入酶安装，由读取蛋白读取，并由擦除酶去除， 它们具有改变RNA结构和动力学的内在能力。他们影响翻译的启动， 终止、翻译保真度、选择性剪接、细胞区室之间运输和调节RNA 降解RNA阅读器、写入器和擦除器蛋白是当前高度关注的有希望的药物靶标， Pharma.尽管如此，目前没有现有的分析方法能够定位多个RNA 修饰同时具有精确的位点信息和化学计量。此应用程序的重点是 降低了RNA修饰分析的位置标记方法的风险，该方法能够多路复用，接近 单碱基分辨率。这项技术将是重要的，因为它将提供第一个商业方法， 在给定的转录组中，跨整个转录组的多种RNA修饰类型的变化的概况分析和关联 sample.