CHEMICAL BASIS OF GROUP II INTRON FUNCTION

II组内含子功能的化学基础

• 批准号: 2640943
• 负责人: JULIANE K STRAUSS-SOUKUP
• 金额: $ 2.5万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-09-17 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2640943
• 关键词: RNA; RNA splicing; chemical structure function; genetic mapping; introns; nucleotide analog; ribozymes

The growing interest in RNA structure has stemmed from the discovery of catalytic RNA molecules that can fold to form active sites for catalysis of chemical reactions. Group II introns are self-splicing RNAs that are equipped to perform the two step transesterification reaction in both the forward and reverse directions. Reverse splicing by the intron can occur into a DNA or RNA substrate. With the assistance of an intron encoded maturase, the group II intron site-specifically inserts itself into duplex DNA. It is of interest to identify the RNA structural elements required for reverse splicing into DNA. Nucleotide Analog Interference Mapping (NAIM) is a novel chemogenetic approach to biochemically characterize RNA structure. After development of a reverse splicing assay, NAIM will be utilized to understand the chemical basis of group II intron structure and function. The interactions identified using NAIM will increase the understanding of group II intron structure and tertiary contacts at the atomic level. The study of group II intron splicing will yield numerous insights into pre-mRNA splicing, since these two processes are similar. High resolution details of the structure of the group II intron during reverse splicing may allow for development of novel site specific vectors that can be used as genetic agents for the treatment of cancer and viral infections.

人们对 RNA 结构日益增长的兴趣源于以下发现： 催化 RNA 分子可以折叠形成催化活性位点 的化学反应。 II 组内含子是自剪接 RNA 配备可在两种设备中进行两步酯交换反应 前进和后退方向。 内含子的反向剪接 发生在 DNA 或 RNA 底物中。 在内含子的帮助下 编码成熟酶，II 组内含子位点特异性插入自身 成双链DNA。 鉴定RNA结构是很有意义的 反向剪接成 DNA 所需的元件。核苷酸类似物 干扰图谱 (NAIM) 是一种新颖的化学遗传学方法 生化表征 RNA 结构。 开发出一个后 反向剪接测定，NAIM 将用于了解化学物质 II组内含子结构和功能的基础。 相互作用 使用 NAIM 鉴定将增加对 II 组内含子的理解 原子水平的结构和三级接触。 团体研究 II 内含子剪接将产生对前 mRNA 剪接的大量见解， 因为这两个过程是相似的。 高分辨率细节 反向剪接过程中第二组内含子的结构可能允许 开发可用作遗传的新型位点特异性载体 用于治疗癌症和病毒感染的药物。