Location: Its role in protein-RNA contact during trypanosome gene regulation

描述（由申请方提供）：锥虫是一种寄生虫，可导致人类和牲畜衰弱，通常是致命性疾病。撒哈拉以南非洲的一个特别严重的问题是由布氏锥虫引起的，这是一种通过受感染的采采蝇叮咬传播的寄生虫。T.布氏杆菌通过在哺乳动物宿主的血液、组织空间以及最终的中枢神经系统中增殖而引起疾病。相关寄生虫对世界其他地区的人群同样重要，包括南美洲和中美洲，东南亚和中东。我们的长期目标是了解，在生化和遗传细节，协调锥虫基因表达的机制。为了实现这一目标，我们正在专门研究寄生虫用于调节其mRNA表达模式的机制。mRNA表达产生特征性和必需的蛋白质组，并决定寄生虫的代谢能力。作为理解mRNA表达控制的途径，我们正在研究一种新的RNA结合蛋白RBP 42，选择它进行研究是因为它（1）对于寄生虫增殖是必需的，（2）结合到编码细胞能量代谢途径中的各种酶和蛋白质的mRNA的编码区（开放阅读框）。我们目前还不知道其他锥虫蛋白具有这种结合特异性;然而，在神经生物学和发育领域，人们越来越认识到编码区结合蛋白。此外，我们的数据表明，RBP 42是mRNA翻译，mRNA稳定性或mRNA螯合的重要因素，因为它结合到多核糖体相关，翻译mRNA在T的前循环阶段。布鲁氏菌的生命周期我们的目标是通过确定RBP 42在T.布鲁塞。这个探索性的，为期两年的项目是基于初步数据，在最近的出版物从我们的实验室，初步数据和补充体内分子遗传学和体外生化方法。

DESCRIPTION (provided by applicant): Trypanosomatids are parasites that cause debilitating and often fatal diseases in humans and livestock. A particularly serious problem in sub-Saharan Africa is caused by Trypanosoma brucei, a parasite spread by the bite of an infected Tsetse fly. T. brucei causes disease by proliferating in the blood, tissue spaces, and eventually the central nervous system of its mammalian host. Related parasites are equally important to human populations in other parts of the world, including South and Central America, Southeastern Asia and the Middle East. Our long-term goal is to understand, in biochemical and genetic detail, the mechanisms that coordinate gene expression in trypanosomatids. To achieve this goal, we are specifically investigating the mechanism used by the parasites to regulate their mRNA expression pattern. mRNA expression gives rise to a characteristic and essential proteome and determines the metabolic capabilities of the parasites. As a pathway into understanding mRNA expression control, we are studying a novel RNA-binding protein, RBP42, which was chosen for investigation because it (1) is essential for parasite proliferation and (2) binds to the coding region (open reading frame) of mRNAs encoding a variety of enzymes and proteins within the cells' energy metabolic pathways. We currently know of no other trypanosome protein with this binding specificity; however there is an increasing awareness of coding region binding proteins in the fields of neurobiology and development. Furthermore, our data suggest that RBP42 is an important factor in mRNA translation, mRNA stability or mRNA sequestration as it binds to polysome-associated, translating mRNAs during the procyclic stage of the T. brucei life-cycle. In our aim, we will explore the function of RBP42 by determining its role and mode of action in gene expression networks of T. brucei. This exploratory, two-year project is grounded in preliminary data, in a recent publication from our laboratory, preliminary data and complementary in vivo molecular genetic and in vitro biochemical approaches.