EXPRESSION OF THE LEISHMANIA TARENTOLAE SL RNA GENE

塔伦托利什曼原虫 SL RNA 基因的表达

• 批准号: 6510655
• 负责人: DAVID A CAMPBELL
• 金额: $ 25.49万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-12-01 至 2004-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6510655
• 关键词: DNA binding protein; DNA directed RNA polymerase; Leishmania; RNA binding protein; RNA biosynthesis; RNA splicing; RNase protection assay; X ray; gel mobility shift assay; gene expression; gene mutation; genetic mapping; genetic promoter element; genetic regulatory element; genetic transcription; microorganism genetics; northern blottings; nucleic acid sequence; polymerase chain reaction; precursor mRNA; protein protein interaction; protein sequence; protein structure function; regulatory gene; tissue /cell culture; transcription factor

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.

利什曼病，非洲睡眠疾病和查加斯病是致命的 或使每年超过2000万人遭受超过2000万人的疾病使人衰弱 在热带国家，是由相关感染引起的 锥虫原生动物。 我们正在研究锥虫的特征 在病原体中共享的基因表达，但 在人类宿主中不存在。 寄生虫剪接的表达 Leader RNA基因及其主要转录本的作用SL RNA在 通过移媒体的核使者RNA（mRNA）的成熟为 我们研究的重点。 我们正在采用分子遗传和 定义指导启动的启动子的生化方法 SL RNA基因转录的构造，并表征结合的蛋白质 到SL RNA基因启动子。 在下一个资金期间，我们建议：1）定义蛋白质-DNA SL RNA基因启动子的转录启动中的相互作用， 并确定转录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 转录终止和有效效率所必需的基因 转录启动，3）分析突变在 剪接的领导者可能会影响翻译。 这些实验将确定新分子并阐明必需品 蛋白-DNA和RNA-RNA相互作用，区分寄生虫的蛋白质 人类宿主的代谢。 这些独特的功能代表 选择性治疗干预的潜在目标。