In silico and biological survey of transcription-associated proteins implicated in the transcriptional machinery during the erythrocytic development of Plasmodium falciparum

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.

A Plasmodium Falciparum Bromodomain Protein Regulates Invasion Gene Expression

“…Differences in histone modifications that contribute to chromatin structure are also associated with the transcriptional activity of several invasion genes (Comeaux et al, 2011;Corté s et al, 2007;Crowley et al, 2011;Jiang et al, 2010). Many histone modifications have been mapped across the P. falciparum genome (Bá rtfai et al, 2010;Cui et al, 2007;Gupta et al, 2013;Jiang et al, 2013;Lopez-Rubio et al, 2009;Salcedo-Amaya et al, 2009), and many proteins with predicted histone-binding domains have been identified bioinformatically (Bischoff and Vaquero, 2010). However, very few factors which bind to modified histones have been characterized (Dastidar et al, 2013;Flueck et al, 2009;Pé rez-Toledo et al, 2009).…”

Plasmodium falciparum Tudor Staphylococcal Nuclease interacting proteins suggest its role in nuclear as well as splicing processes

“…In silico and biological analyses have identified four functional classes of Transcription Associated Proteins (TAPs) in the Plasmodium genome; general transcription factors which include all the polymerases, initiation and elongation factors, factors involved in the chromatinstructuring and remodeling, chromatin-related transcription factors (CTFs) and finally the specific transcription factors (STFs) such as ApiAp2, PfMyb1 etc. (Bischoff and Vaquero, 2010). We have recently described a family of RNA binding proteins, the 'tudor domain protein family' in the human malaria parasite, P. falciparum and identified a plasmodial homolog of the human p100 protein, termed PfTudor-SN.…”

Landscape and Dynamics of Transcription Initiation in the Malaria Parasite Plasmodium falciparum

“…Indeed, the majority of the ∼5500 genes vary significantly in steady-state mRNA levels between the different intra-erythrocytic stages, resulting in a developmentally-linked cascade of gene expression. Genome surveys showed conservation of the basal eukaryotic transcriptional machinery, but also suggested a paucity of transcription-associated factors (Bischoff and Vaquero, 2010; Callebaut et al, 2005; Coulson et al, 2004). Despite major advances comprising the identification of transcription factors that govern P. falciparum stage-specific gene expression (Balaji, 2005; De Silva et al, 2008), the lack of a comprehensive map of transcription initiation events has hampered advances in decrypting the molecular basis of transcriptional control.…”