Biochemische Charakterisierung der Ribonukleoprotein-vermittelten Mobiliät von non-LTR-Retrotransposons

非LTR反转录转座子是一种移动的遗传元件，存在于几乎所有的真核生物中。它们对基因组可塑性的无与伦比的影响和它们精心制作的RNA介导的复制机制（靶向启动逆转录，TPRT）使它们成为从进化和生物化学角度研究的重要课题。在这项研究中，我将建立一个新的模型系统，以生化特性的RNA/蛋白质机器进行反转录转座过程。通过化学修饰和交联实验探测这种核糖核蛋白复合物的结构，我将绘制RNA/蛋白质界面。机制研究将涉及使用各种不同底物的逆转录过程的深入动力学分析。这项研究的结果将揭示基因组的大部分是如何产生的，并使我们能够更好地操纵逆转录转座子用于生物技术和医学目的。此外，与端粒酶和II组内含子等相关系统的比较将为我们提供新的见解，了解RNA和蛋白质如何合作以及它们如何在进化过程中改变功能。

Non-LTR retrotransposons are mobile genetic elements found in almost every eukarotic organism. Their unparalleled impact on genome plasticity and their elaborate RNA-mediated replication mechanism (target primed reverse transcription, TPRT) make them important subjects of study both from an evolutionary and biochemical point of view. In this study, I will set up a new model system to biochemically characterize the RNA/protein machinery that performs the retrotransposition process. By probing the structure of this ribonucleoprotein complex with chemical modification and crosslinking experiments, I will map the RNA/protein interface. Mechanistic studies will involve in-depth kinetic analysis of the reverse transcription process using a variety of different substrates. The results of this study will shed light on how large portions of the genome are generated and enable us to better manipulate retrotransposons for biotechnological and medical purposes. Besides, comparison with related systems like telomerases and group II introns will provide us with new insights into how RNA and proteins cooperate and how they change their functions during evolution.