Abstract

BackgroundRegulation of gene expression in Plasmodium falciparum (Pf) remains poorly understood. While over half the genes are estimated to be regulated at the transcriptional level, few regulatory motifs and transcription regulators have been found.ResultsThe study seeks to identify putative regulatory motifs in the upstream regions of 13 functional groups of genes expressed in the intraerythrocytic developmental cycle of Pf. Three motif-discovery programs were used for the purpose, and motifs were searched for only on the gene coding strand. Four motifs – the 'G-rich', the 'C-rich', the 'TGTG' and the 'CACA' motifs – were identified, and zero to all four of these occur in the 13 sets of upstream regions. The 'CACA motif' was absent in functional groups expressed during the ring to early trophozoite transition. For functional groups expressed in each transition, the motifs tended to be similar. Upstream motifs in some functional groups showed 'positional conservation' by occurring at similar positions relative to the translational start site (TLS); this increases their significance as regulatory motifs. In the ribonucleotide synthesis, mitochondrial, proteasome and organellar translation machinery genes, G-rich, C-rich, CACA and TGTG motifs, respectively, occur with striking positional conservation. In the organellar translation machinery group, G-rich motifs occur close to the TLS. The same motifs were sometimes identified for multiple functional groups; differences in location and abundance of the motifs appear to ensure different modes of action.ConclusionThe identification of positionally conserved over-represented upstream motifs throws light on putative regulatory elements for transcription in Pf.

Highlights

  • Regulation of gene expression in Plasmodium falciparum (Pf) remains poorly understood

  • It is believed to be likely that genes with similar mRNA expression profiles are regulated via the same mechanism; it is thought to be likely that genes with similar functions are regulated by the same mechanism

  • In the asexual intraerythrocytic developmental cycle (IDC) transcriptome of Pf, it has been shown that cellular processes take place in an orderly, programmed and continuous cascade, and that functionally related genes along this cascade show similar expression profiles [3]

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Summary

Introduction

Regulation of gene expression in Plasmodium falciparum (Pf) remains poorly understood. The life-cycle of the malarial parasite, Plasmodium falciparum (Pf), consists of several morphological forms which occur in the mosquito, liver and blood stages (e.g., gamete, salivary gland sporozoite, ring, trophozoite, schizont, merozoite, gametocyte). Pf generates these morphologies by regulating its gene expression; the morphological transformations are accompanied by changes in the RNA and protein repertoires of the cell [1,2]. Co-expressed genes which have similar functions are more likely to be co-regulated [4] They are likely to have conserved DNA sequence elements, called transcription factor binding motifs (TFBMs), in their promoter regions. In response to environmental and developmental cues, TFBMs are bound by their cognate transcription factors, and, as a result, co-expression of the associated set of genes takes place, by activation or inhibition of the transcription machinery [4,5,6,7]

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