Rapid NGS Method for Mapping of the Epitranscriptome

项目摘要/摘要 表观转录组学是对RNA修饰的研究，其中包括170多种自然产生的化学物质 核苷酸的变化。在人类各种类型的RNA中发现了60多种：mRNA、tRNA、rRNA、lncRNA、 还有其他人。这些修改是动态的；它们的全球数量在开发过程中和 疾病的发展。它们由编写器酶安装，由阅读器蛋白质读取，并被橡皮擦去除 酶，它们具有改变RNA结构和动力学的内在能力。他们影响翻译 起始和终止、翻译保真度、可选剪接、细胞隔间之间的传输，以及 调节RNA降解。RNA阅读器、写入器和擦除器蛋白是大电流的潜在药物靶点 对制药公司感兴趣。在本项目中，我们将测试和验证一种新的检测、识别和映射方法 多重且高灵敏度的RNA修饰--适用于临床样本(例如，针刺活检， FFPE样品)，其中可能只有亚纳克量的RNA可用。这项技术将是 意义重大，因为它将提供第一种商业方法来分析和关联多个 使用低样本输入，整个转录组的RNA修饰类型。

Project Summary/Abstract Epitranscriptomics is the study of RNA modifications, which include more than 170 naturally occurring chemical alternations to the nucleotides. More than 60 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. In this project, we will test and validate a new approach to detecting, identifying, and mapping RNA modifications in a multiplex and with high sensitivity—suitable for clinical samples (e.g. needle biopsies, FFPE samples) in which only sub-nanogram quantities of RNA may be available. 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 using low sample input.