Abstract
BackgroundTo date, only a few transcription factors have been identified in the genome of the parasite Plasmodium falciparum, the causative agent of malaria. Moreover, no detailed molecular analysis of its basal transcription machinery, which is otherwise well-conserved in the crown group of eukaryotes, has yet been reported. In this study, we have used a combination of sensitive sequence analysis methods to predict the existence of several parasite encoded general transcription factors associated with RNA polymerase II.ResultsSeveral orthologs of general transcription factors associated with RNA polymerase II can be predicted among the hypothetical proteins of the P. falciparum genome using the two-dimensional Hydrophobic Cluster Analysis (HCA) together with profile-based search methods (PSI-BLAST). These predicted orthologous genes encoding putative transcription factors include the large subunit of TFIIA and two candidates for its small subunit, the TFIIE β-subunit, which would associate with the previously known TFIIE α-subunit, the TFIIF β-subunit, as well as the p62/TFB1 subunit of the TFIIH core. Within TFIID, the putative orthologs of TAF1, TAF2, TAF7 and TAF10 were also predicted. However, no candidates for TAFs with classical histone fold domain (HFD) were found, suggesting an unusual architecture of TFIID complex of RNA polymerase II in the parasite.ConclusionTaken together, these results suggest that more general transcription factors may be present in the P. falciparum proteome than initially thought. The prediction of these orthologous general transcription factors opens the way for further studies dealing with transcriptional regulation in P. falciparum. These alternative and sensitive sequence analysis methods can help to identify candidates for other transcriptional regulatory factors in P. falciparum. They will also facilitate the prediction of biological functions for several orphan proteins from other apicomplexan parasites such as Toxoplasma gondii, Cryptosporidium parvum and Eimeria.
Highlights
To date, only a few transcription factors have been identified in the genome of the parasite Plasmodium falciparum, the causative agent of malaria
The use of the sensitive Hydrophobic Cluster Analysis (HCA) in combination with profilebased search methods suggests that the genome of P. falciparum contains several gene products annotated as hypothetical proteins, which can be predicted as putative general transcription factors (GTF) associated with RNA polymerase II (RNAP II)
We have shown that more general transcription factors can be predicted in the genome of P. falciparum than initially thought
Summary
Only a few transcription factors have been identified in the genome of the parasite Plasmodium falciparum, the causative agent of malaria. The lethal form of human malaria is caused by the infection with the obligate intracellular protozoan parasite Plasmodium falciparum, which displays a developmental life cycle alternating between a vertebrate and an invertebrate host. Infection by the sporozoite form of the parasite occurs after the female Anopheles mosquito's bite. For completion of the host-vector cycle, some intra-erythrocytic asexual forms do not undergo schizogony but transform into sexually dimorphic male and female gametocytes upon differentiation. Gametocytes are taken into the mosquito's midgut during a blood meal and complete their sexual development to gametes which will fuse to form a motile zygote named the ookinete. The ookinete grows into an oocyst, dividing into numerous sporozoites that will invade the salivary glands of the mosquito ready for a new cycle of infection [1]
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