EXPRESSION OF THE LEISHMANIA TARENTOLAE SL RNA GENE

利什曼病、非洲昏睡病和恰加斯病是致命的 或使人衰弱的疾病，每年折磨着两千万人 在热带国家，是由感染相关的 锥虫原生动物。 我们正在研究锥虫的特征 这些基因表达在病原体之间共享，但 在人类宿主中是不存在的 寄生虫剪接体的表达 前导RNA基因及其主要转录物SL RNA在 核信使RNA（mRNA）通过反式剪接的成熟是 我们研究的重点。 我们将分子遗传学和 确定指导起始的启动子的生物化学方法 的SL RNA基因转录，并表征结合 SL RNA基因启动子。 在下一个资助期内，我们建议：1）定义蛋白质-DNA 从SL RNA基因启动子转录起始的相互作用， 并鉴定转录SL RNA基因的RNA聚合酶 通过遗传学方法，2）定义SL RNA的其他区域 转录终止所必需的基因， 转录起始，和3）分析突变的影响， 可能影响平移的拼接引线。 这些实验将识别新的分子并阐明关键的 蛋白质-DNA和RNA-RNA相互作用，区分寄生虫的 与人类宿主的新陈代谢不同 这些独特的特征代表了 选择性治疗干预的潜在目标。

Leishmaniasis, African Sleeping Sickness and Chagas Disease are fatal or debilitating diseases that afflict over 20 million people annually in tropical countries and are caused by infections with related trypanosomatid protozoa. We are studying features of trypanosomatid gene expression that are shared among the pathogens, but which are absent in the human host. The expression of the parasite's Spliced Leader RNA gene and the role of its primary transcript, the SL RNA, in the maturation of nuclear messenger RNAs (mRNA) via trans-splicing is the focus of our research. We are taking molecular genetic and biochemical approaches to defining the promoter that directs initiation of SL RNA gene transcription, and characterizing protein(s) that bind to the SL RNA gene promoter. In the next funding period we propose to: 1) define the protein-DNA interactions in transcription initiation from the SL RNA gene promoter, and to identify the RNA polymerase that transcribes the SL RNA gene through a genetic approach, 2) define additional regions of the SL RNA gene that are necessary for transcription termination and efficient transcription initiation, and 3) analyze the effect of mutations in the Spliced Leader that may affect translation. These experiments will identify new molecules and elucidate essential protein-DNA and RNA-RNA interactions that distinguish the parasite's metabolism from that of the human host. These unique features represent potential targets for selective therapeutic intervention.