In silico and biological survey of transcription-associated proteins implicated in the transcriptional machinery during the erythrocytic development of Plasmodium falciparum.
In silico and biological survey of transcription-associated proteins implicated in the transcriptional machinery during the erythrocytic development of Plasmodium falciparum.
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DOI：
10.1186/1471-2164-11-34
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发表时间：
2010-01-15
期刊：
影响因子：
4.4
通讯作者：
Vaquero C
中科院分区：
文献类型：
--
作者：
Bischoff E;Vaquero C
疟疾是世界上最重要的寄生虫病，每年约有200万人死亡，主要死于恶性疟原虫感染。在按蚊媒介和人类宿主的复杂生命周期中，寄生虫需要参与表观遗传、转录和转录后调控的多种基因的协调和调节表达。然而，尽管恶性疟原虫基因组的完整序列已经确定，但我们对疟原虫转录基因调控的机制仍然知之甚少。这是由于对核蛋白、同源DNA基序和转录结构的预测较差。从所有的计算机报告和数据库中建立了一个全面的蛋白质目录，这些蛋白质被报道可能参与疟原虫的转录机制。转录相关蛋白聚集在三组主要因子中：一般转录因子，染色质相关蛋白（结构，重塑和组蛋白修饰酶）和特异性转录因子。这些因素中只有少数被分子分析过。此外，根据转录组和蛋白质组数据，我们模拟了红细胞内周期中转录本和相应蛋白质的表达模式。最后，讨论了基于硅或2-酵母杂交实验方法的这些蛋白质的相互作用组。这是首次尝试建立疟原虫潜在转录相关蛋白的综合目录。此外，我们对所有完整的转录组、蛋白质组和相互作用组原始数据进行了重新分析、比较和讨论，以便更好地理解恶性疟原虫在红细胞发育过程中转录调控的复杂生物学过程。
Malaria is the most important parasitic disease in the world with approximately two million people dying every year, mostly due to Plasmodium falciparum infection. During its complex life cycle in the Anopheles vector and human host, the parasite requires the coordinated and modulated expression of diverse sets of genes involved in epigenetic, transcriptional and post-transcriptional regulation. However, despite the availability of the complete sequence of the Plasmodium falciparum genome, we are still quite ignorant about Plasmodium mechanisms of transcriptional gene regulation. This is due to the poor prediction of nuclear proteins, cognate DNA motifs and structures involved in transcription. A comprehensive directory of proteins reported to be potentially involved in Plasmodium transcriptional machinery was built from all in silico reports and databanks. The transcription-associated proteins were clustered in three main sets of factors: general transcription factors, chromatin-related proteins (structuring, remodelling and histone modifying enzymes), and specific transcription factors. Only a few of these factors have been molecularly analysed. Furthermore, from transcriptome and proteome data we modelled expression patterns of transcripts and corresponding proteins during the intra-erythrocytic cycle. Finally, an interactome of these proteins based either on in silico or on 2-yeast-hybrid experimental approaches is discussed. This is the first attempt to build a comprehensive directory of potential transcription-associated proteins in Plasmodium. In addition, all complete transcriptome, proteome and interactome raw data were re-analysed, compared and discussed for a better comprehension of the complex biological processes of Plasmodium falciparum transcriptional regulation during the erythrocytic development.
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