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The role of Pumilio-domain proteins in Trypanosoma brucei

Pumilio 结构域蛋白在布氏锥虫中的作用

基本信息

批准号：
152065058
负责人：
Professorin Dr. Christine Elizabeth Clayton
金额：
--
依托单位：
Zentrum für Molekulare Biologie (ZMBH)
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2009
资助国家：
德国
起止时间：
2008-12-31 至 2013-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/152065058?language=en
关键词：
role Pumilio domain proteins Trypanosoma

项目摘要

Proteins with Pumilio (Puf) RNA-binding domains play important roles in control of eukaryotic gene expression. Puf proteins bind specific motifs in the 3’-untranslated regions of mRNAs; usually, this results in translation inhibition and mRNA degradation, but in most cases the mechanisms are unknown. In Kinetoplastid protozoa, nearly all control of gene expression is post-transcriptional: therefore, regulated mRNA degradation is essential for parasite survival. The enzymes that degrade mRNAs in the Kinetoplastid Trypanosoma brucei are well described, but the mechanisms by which they are controlled are unknown. This application concerns the roles of two trypanosome Puf-domain proteins, PUF5 and PUF9, in trypanosome gene regulation; the information obtained is likely to provide general insights into the functions of Puf proteins in eukaryotes. Trypanosome PUF9 stabilises four mRNAs during the S phase of the cell cycle, and this requires a specific sequence motif in the mRNA 3’-untranslated region. Evidence suggests that PUF9 antagonises another, destabilising protein: the most likely candidate is PUF5. Preliminary data indicate that PUF5 promotes mRNA degradation. Analysis of PUF5 and PUF9 will include assessment of the effect of downregulation or over-expression on trypanosome growth and the transcriptome, monitoring expression and activity throughout the cell cycle, detailed determination of RNA binding specificity, and investigating how the proteins control mRNA levels.

具有Puf rna结合结构域的蛋白在真核生物基因表达调控中起重要作用。Puf蛋白在mrna的3 ' -非翻译区结合特异性基序；通常，这导致翻译抑制和mRNA降解，但在大多数情况下，其机制尚不清楚。在动着质体原生动物中，几乎所有基因表达的控制都是转录后的：因此，调节mRNA降解对寄生虫的生存至关重要。胞浆体布鲁氏锥虫中降解mrna的酶已被很好地描述，但它们被控制的机制尚不清楚。该应用涉及两种锥虫puf结构域蛋白PUF5和PUF9在锥虫基因调控中的作用；所获得的信息很可能为真核生物中Puf蛋白的功能提供一般的见解。锥虫PUF9在细胞周期的S期稳定4种mRNA，这需要mRNA 3 ' -非翻译区有一个特定的序列基序。有证据表明，PUF9可以对抗另一种破坏稳定的蛋白质：最有可能的候选者是PUF5。初步数据表明PUF5促进mRNA降解。对PUF5和PUF9的分析将包括评估下调或过表达对锥虫生长和转录组的影响，监测整个细胞周期的表达和活性，详细确定RNA结合特异性，并研究蛋白质如何控制mRNA水平。