Characterization of a Non-Spliceosomal mRNA Ligase

描述(申请人提供)：信使核糖核酸反式连接现象是一个知之甚少的过程，需要新的实验技术和洞察力。这项提议将研究人类癌细胞中发现的对临床相关核糖核酸酶治疗的反应的信使核糖核酸反式连接。核糖核酸酶诱导的mRNA反式连接的程度将通过RNA测序技术来表征。一种被认为负责观察到的信使核糖核酸连接的酶将从动力学和力学上进行表征。结合细胞研究和体外表征的信使核糖核酸连接将揭示这一未知的生理过程的重要细节。对mRNA反式连接的基本了解可能会导致对各种正常的生理和疾病过程的理解。

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.