Characterization of a Non-Spliceosomal mRNA Ligase

非剪接体 mRNA 连接酶的表征

• 批准号: 8436408
• 负责人: Kevin K Desai
• 金额: $ 5.22万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-02-01 至 2015-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8436408
• 关键词: Archaea; Cell Cycle; Cells; Cleaved cell; DNA Ligases; Detection; Disease; Enzymes; Escherichia coli; Exons; Genes; Histones; Human; Hydroxyl Radical; In Vitro; Incubated; K-562; Kinetics; Lead; Life; Ligase; Ligation; Mammalian Cell; Mammals; Messenger RNA; Molecular; Myeloid Leukemia; Pathway interactions; Physiological; Physiological Processes; Play; Process; Production; RNA; RNA Interference; RNA Ligase (ATP); RNA Sequences; Research; Ribonucleases; Role; Substrate Specificity; Techniques; Transfer RNA; Work; cancer cell; clinically relevant; design; enzyme mechanism; in vivo; inhibitor/antagonist; inorganic phosphate; insight; novel; reconstitution; repaired; response; transcriptome sequencing

DESCRIPTION (provided by applicant): The phenomenon of mRNA trans-ligation is a poorly understood process in need of novel experimental techniques and insight. This proposal will study mRNA trans-ligation in human cancer cells that was discovered as a response to treatment with a clinically relevant ribonuclease. The extent of mRNA trans- ligation induced by ribonucleases will be characterized by RNA sequencing techniques. An enzyme hypothesized to be responsible for the observed mRNA ligation will be characterized kinetically and mechanistically. A combination of cellular studies and in vitro characterizations of mRNA ligation will bring to light important details about this uncharacterized physiological process. A fundamental understanding of mRNA trans-ligation is likely to lead to an understanding of various normal physiological and disease processes.

描述（由申请人提供）：mRNA转连接现象是一个了解甚少的过程，需要新的实验技术和见解。该提案将研究人类癌细胞中的mRNA转连接，该转连接被发现是对临床相关核糖核酸酶治疗的反应。由核糖核酸酶诱导的mRNA反式连接的程度将通过RNA测序技术表征。假设负责观察到的mRNA连接的酶将在动力学和机制上表征。结合细胞研究和体外表征的mRNA连接将带来光的重要细节，这个未知的生理过程。对mRNA trans-ligation的基本理解可能会导致对各种正常生理和疾病过程的理解。