Abstract
BackgroundMalaria 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.ResultsA 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.ConclusionThis 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.
Highlights
Malaria is the most important parasitic disease in the world with approximately two million people dying every year, mostly due to Plasmodium falciparum infection
Since a number of reports showed that the transcriptome profiles change [6,7] during the parasite erythrocytic development, it was reasonable to assume that different sets of TranscriptionAssociated Protein (TAP) were essential to govern the fine tuning of transcriptional regulation during the erythrocytic cycle
Coulson and collaborators [12] used two strategies to identify the Treanscription Factor (TF) of P. falciparum: 51 Hidden Markov Model (HMM) profiles from TRANSFAC and a sequence similarity clustering method were used to identify 156 TAP including specific transcription factors in the P. falciparum genome
Summary
Malaria is the most important parasitic disease in the world with approximately two million people dying every year, mostly due to Plasmodium falciparum infection. 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. Regulation of gene expression of this unicellular eukaryote is probably governed, as for all eukaryotes, by common mechanisms including epigenetic, transcriptional as well as post-transcriptional regulation. If a small number of specific transcription factors is a real characteristic of Plasmodium, this might in turn account for the unusual mechanisms of gene regulation involving a major contribution of epigenetic and post-transcriptional machineries [10]. The high A/T rich genome probably contributes to this poor annotation due to a weak similarity of Plasmodium factors with the amino acid sequences of eukaryotic proteins listed in DataBanks including TRANSFAC® the Transcription Factor Database [13]
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