Molecular mechanisms of hereditary thrombophilia: physiological function of prothrombin mRNA 3` end maturation

凝血酶原或凝血因子II基因（F2） 20210位点的G A突变影响约1-2%的西北欧人口，导致血栓栓塞事件风险增加3-5倍，因此被认为是一个公共卫生问题。在临床研究中，这种增加的风险与受影响个体的凝血酶原血浆浓度升高有关。然而，这种突变的分子机制尚不清楚。在我们工作的第一阶段，我们确定这种突变导致3 '端RNA加工功能的获得，这代表了遗传疾病分子发病机制的新原理。我们现在计划从功能上描述这种新的分子机制，从而在医学上获得与RNA成熟功能高度相关的增益，并旨在深入了解不同水平的3 '端加工效率的生理含义。

The G A mutation at position 20210 of the prothrombin or coagulation factor II gene (F2) affects about 1-2% of the north-west European population and results in a 3-5-fold increase of the risk of thromboembolic events and is therefore considered to be of public health concern. In clinical studies, this increased risk has been associated with an elevated prothrombin plasma concentration in affected individuals. However, the molecular mechanism of this mutation has been unknown. In the first phase of our work, we established that this mutation results in a gain of function of 3` end RNA processing, which represents a novel principle for the molecular pathogenesis of a genetic disorder. We now plan to functionally charaterise this novel molecular mechanism that results in a medically highly relevant gain of function of RNA maturation and aim to obtain insight into the physiological implications of different levels of 3` end processing efficiency.