Identification and characterization of transcription co-factor multiprotein bridging factor-1 in Plasmodium

Sumit Kumar

doi:10.17918/00009602

The most severe form of human malaria is caused by infection with the unicellular apicomplexan parasite Plasmodium falciparum and despite its impact on global health, our understanding of many aspects of the parasite's biology is still in its infancy. Compared with model eukaryotic systems, our knowledge of processes as fundamental as sexual differentiation, gene expression and protein trafficking in Plasmodium is severely lacking. The belief that mechanisms of transcriptional control in P. falciparum somehow differ from those of other eukaryotes is, in large part, based on several genome-wide studies that uncovered significantly fewer transcription-associated proteins (TAPs) than one would expect to find in a genome of comparable size. Other findings, including a dearth of well-conserved promoter elements, unusually high levels of antisense transcription, unique patterns of mRNA decay and a striking, periodic transcriptional cascade, also support this hypothesis. These hypotheses, however, may have to be re-assessed in light of the recent discoveries of several cis-regulatory elements and an expanded family of plantlike transcription factors in Plasmodium. In either case, it is clear that precise regulation of transcription in the parasite is critical. In the work presented here, we have successfully identified and characterized PfMBF-1 (Multiprotein bridging factor-1), which is a well studied transcription co-factor in other eukaryotic species. It does not affect histone modification, but rather acts as a bridging factor between a DNA-binding protein and the entire TFIID complex [TBP and TAFs (TBP-associated factors)]. Our studies show that PfMBF-1 is essential for the parasite survival during the blood stages and it is involved in stage specific transcriptional regulation. Overexpression of PfMBF-1 upregulates specific set of genes which are proposed to be rhoptry associated genes. We have shown in vitro that PfMBF-1 specifically interacts with PfTBP and it is localized in nucleus of the parasite. PfMBF-1 successfully complements the function of yeast MBF-1 and further confirms its ability to act as transcriptional co-factor. We have identified DNA motifs which might be critical in the expression and regulation of Plasmodium genes. We believe that elucidating the role of this transcription co-factor MBF-1 will provide crucial information for enhanced understanding of parasite gene expression regulation and help to discover new transcriptional regulators.

Identification and characterization of transcription co-factor multiprotein bridging factor-1 in Plasmodium

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Identification and characterization of transcription co-factor multiprotein bridging factor-1 in Plasmodium

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