Identification of a Novel and Unique Transcription Factor in the Intraerythrocytic Stage of <i>Plasmodium falciparum</i>

<div><p>The mechanisms of stage-specific gene regulation in the malaria parasite <i>Plasmodium falciparum</i> are largely unclear, with only a small number of specific regulatory transcription factors (AP2 family) having been identified. In particular, the transcription factors that function in the intraerythrocytic stage remain to be elucidated. Previously, as a model case for stage-specific transcription in the <i>P. falciparum</i> intraerythrocytic stage, we analyzed the transcriptional regulation of <i>pf1-cys-prx</i>, a trophozoite/schizont-specific gene, and suggested that some nuclear factors bind specifically to the <i>cis</i>-element of <i>pf1-cys-prx</i> and enhance transcription. In the present study, we purified nuclear factors from parasite nuclear extract by 5 steps of chromatography, and identified a factor termed PREBP. PREBP is not included in the AP2 family, and is a novel protein with four K-homology (KH) domains. The KH domain is known to be found in RNA-binding or single-stranded DNA-binding proteins. PREBP is well conserved in <i>Plasmodium</i> species and partially conserved in phylum Apicomplexa. To evaluate the effects of PREBP overexpression, we used a transient overexpression and luciferase assay combined approach. Overexpression of PREBP markedly enhanced luciferase expression under the control of the <i>pf1-cys-prx cis</i>-element. These results provide the first evidence of a novel transcription factor that activates the gene expression in the malaria parasite intraerythrocytic stage. These findings enhance our understanding of the evolution of specific transcription machinery in <i>Plasmodium</i> and other eukaryotes.</p>