RNA-protein complexes in trypanosomes

锥虫中的 RNA-蛋白质复合物

• 批准号: 6925526
• 负责人: ALBERTO CARLOS FRASCH
• 金额: $ 8.1万
• 依托单位: INSTITUTE/RESEARCH/BIOTECHNOLOGY FDN
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6925526
• 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

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）：Cruzi锥虫是美洲和Brucei spp的Chagas疾病的推动者。是人类熟睡的原因，而在动物中纳加纳的疾病。锥虫以及像利什曼原虫（Leishmania spp。然而，在转录开始时对基因表达的控制是从细菌到哺乳动物细胞的最常见和高度使用的机制，在锥虫中可能无关。因此，转录后机制对于寄生虫阶段的发展和宿主的生存似乎至关重要。因此，锥虫构成了一个有趣的模型细胞，用于研究转录后事件，导致转录本翻译/降解，可用于开发疾病控制的替代方法。包括我们组在内的几个组的结果表明，mRNA半衰期在基因表达中的调节重要性。该过程涉及转录和RNA结合蛋白的动机，这两者都形成了核糖核蛋白络合物的一部分，可以检测到“体内”。假设是这些络合物的不同组成使转录本易于破坏/降解或转化为蛋白质的长期物体，并且是蛋白质的长期目标。为此目的，在寄生虫发育过程中，核糖蛋白在mRNA途径中的复合物及其组成如何导致寄生虫的降解/翻译将研究寄生虫发育过程中的核糖蛋白复合物的相关性。