Positional Marking of RNA Modifications

RNA 修饰的位置标记

基本信息

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
项目类别：
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

项目摘要

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 RNA修饰构成了表面翻译，在RNA的所有方面都起着至关重要的作用代谢和RNA在中央教条中的作用。超过170多个自然发生的化学修饰 RNA是已知的，其中60多个在所有类型的人RNA中都发现：mRNA，tRNA，rRNA，lncRNA和其他。这些修改是动态的。它们的全球发展和疾病期间的变化进展。它们由作者酶安装，由读取器蛋白读取，并由Eraser酶去除，它们具有改变RNA结构和动力学的内在能力。它们影响翻译的启动和终止，翻译保真度，替代剪接，细胞室之间的运输和调节RNA 降解。 RNA读取器，作家和橡皮蛋白是有希望的药物靶标，具有高电流的兴趣制药。尽管有这种意义，但目前没有现有的分析方法能够定位多个RNA 简单地使用精确的基因座信息和化学计量法进行修改。该应用的重点是 DE危风险的RNA修饰分析的位置标记方法，该方法能够多路复用，接近单基础分辨率。该技术将是重要的，因为它将为在给定的整个转录组中的多种RNA修饰类型的分析和关联样本。