RNA-protein complexes in trypanosomes

锥虫中的 RNA-蛋白质复合物

基本信息

批准号：
7106642
负责人：
ALBERTO CARLOS FRASCH
金额：
$ 7.91万
依托单位：
INSTITUTE/RESEARCH/BIOTECHNOLOGY FDN
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-08-01 至 2008-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7106642
关键词：
DNA directed RNA polymerase RNA binding protein Trypanosoma cruzi antibody gene expression gene targeting genetic regulation genetic regulatory element laboratory rabbit posttranscriptional RNA processing protein protein interaction protein structure function

项目摘要

DESCRIPTION (provided by the applicant): Trypanosoma cruzi is the agent of Chagas' disease in the Americas and T. brucei spp. is the cause of sleeping sickness in humans and nagana in animals. Trypanosomes, as well as trypanosomatids like Leishmania spp., have to tightly regulate gene expression to adapt to different environments in vertebrate and insect hosts. However, control of gene expression at transcription initiation, the most frequent and highly used mechanism from bacteria to mammalian cells, is likely to be not relevant in Trypanosomes. Thus, post-transcriptional mechanisms seem essential for the development of parasite stages and survival in the hosts. As a consequence, trypanosomes constitute an interesting model cell to study post-transcriptional events leading to transcript translation/degradation that could be used to develop alternatives for disease control. Results from several groups, including our group, suggest the importance of the modulation of mRNA half-life in gene expression. This process involves motives in the transcript and RNA-binding proteins, both forming part of ribonucleoprotein complexes which can be detected "in vivo'. The hypothesis is that the different composition of these complexes renders the transcript prone for destabilization/degradation or translation into a protein. The long-term objectives of the work proposed are the characterization of mRNAs and RNA-binding proteins in different ribonucleoprotein complexes during the mRNA pathway and how their composition results in transcript degradation/translation during parasite development. For this purpose, the mRNAs present in specific ribonucleoprotein complexes bearing previously characterized RNA-binding proteins will be identified. Then, protein partners of known RNA-binding proteins present in ribonucleoprotein complexes "in vivo" will be characterized. Finally, the biological relevance of ribonucleoprotein complexes during parasite development will be studied. Parasites knocked-out/over-expressing a RNA-binding protein will be constructed to analyze the fate of transcripts. The information obtained will contribute to the understanding of a relevant process for trypanosome survival and to the identification of potential targets for unconventional drug development.

描述（由申请人提供）：克氏锥虫是美洲恰加斯病和布氏锥虫属的病原体。是人类昏睡病和动物那加那病的原因。锥虫以及利什曼原虫等锥虫必须严格调节基因表达，以适应脊椎动物和昆虫宿主的不同环境。然而，转录起始时基因表达的控制（从细菌到哺乳动物细胞最常见和最常用的机制）可能与锥虫无关。因此，转录后机制似乎对于寄生虫阶段的发育和宿主的生存至关重要。因此，锥虫构成了一个有趣的模型细胞，用于研究导致转录物翻译/降解的转录后事件，可用于开发疾病控制的替代方案。包括我们小组在内的几个小组的结果表明了 mRNA 半衰期调节在基因表达中的重要性。这个过程涉及转录物和 RNA 结合蛋白的动机，两者都形成核糖核蛋白复合物的一部分，可以在“体内”检测到。假设是这些复合物的不同组成使得转录物易于不稳定/降解或翻译成这项工作的长期目标是表征 mRNA 通路中不同核糖核蛋白复合物中的 mRNA 和 RNA 结合蛋白，以及它们的组成如何导致转录本降解/翻译。为此，将鉴定存在于具有先前表征的RNA结合蛋白的特定核糖核蛋白复合物中的mRNA，然后，将鉴定存在于“体内”核糖核蛋白复合物中的已知RNA结合蛋白的蛋白质伴侣。将研究寄生虫发育过程中核糖核蛋白复合物的生物学相关性，将构建敲除/过度表达RNA结合蛋白的寄生虫来分析转录物的命运。获得的信息将有助于了解锥虫生存的相关过程，并有助于确定非常规药物开发的潜在靶点。