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.

项目摘要/摘要 构成表位转录组的RNA修饰，似乎在RNA的各个方面都起着至关重要的作用 新陈代谢与核糖核酸在中枢神经系统中的作用170多种自然发生的化学修饰 RNA是已知的，其中60多种存在于人类各种类型的RNA中：mRNA、tRNA、rRNA、lncRNA和 其他人。这些修饰是动态的；它们的全球数量在发育和疾病期间发生变化 进步。它们由写入器酶安装，由阅读器蛋白质读取，并由橡皮擦酶去除， 它们具有改变RNA结构和动态的内在能力。他们影响翻译的启动和 终止、翻译保真度、选择性剪接、细胞间隔室之间的运输和调节RNA 退化。RNA阅读器、写入器和擦除器蛋白是目前最受关注的药物靶标 帕尔玛。尽管有这种重要性，目前存在的任何分析方法都不能定位多个RNA 与精确的轨迹信息和化学计量学同时进行修饰。此应用程序的重点是 一种用于RNA修饰分析的位置标记方法，该方法能够多路、接近 单基分辨率。这项技术将具有重要意义，因为它将为 在给定的转录组中分析和关联跨整个转录组的多种RNA修饰类型的变化 样本。