EXPRESSION OF THE LEISHMANIA TARENTOLAE SL RNA GENE

利什曼病、非洲睡眠病和恰加斯病是致命的 或每年折磨2000多万人的衰弱疾病 在热带国家，由感染相关病毒引起 锥虫原虫。我们正在研究锥虫的特征 在病原体之间共享的基因表达，但 在人类宿主中不存在。寄生虫剪接蛋白的表达 Leader RNA基因及其初级转录产物SL RNA在植物生长发育中的作用 核信使RNA(MRNA)通过反式剪接而成熟 这是我们研究的重点。我们正在利用分子遗传学和 确定引导启动的启动子的生化方法 对SL RNA基因转录的影响，以及结合蛋白(S)的特性 至SL RNA基因启动子。 在下一个资助期，我们建议：1)定义蛋白质-DNA SL RNA基因启动子在转录启动中的相互作用 并鉴定转录SL RNA基因的RNA聚合酶 通过遗传方法，2)定义SL RNA的其他区域 转录终止所必需并有效的基因 转录启动，以及3)分析突变对基因的影响。 可能会影响平移的拼接引线。 这些实验将识别新的分子，并阐明 区分寄生虫的蛋白质-DNA和RNA-RNA相互作用 新陈代谢与人类宿主的新陈代谢。这些独特的特征代表了 选择性治疗干预的潜在靶点。

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.