Comparative Genomics of Transcriptional Control in the Human Malaria Parasite Plasmodium falciparum

Abstract

The life cycle of the parasite Plasmodium falciparum, responsible for the most deadly form of human malaria, requires specialized protein expression for survival in the mammalian host and insect vector. To identify components of processes controlling gene expression during its life cycle, the malarial genome-along with seven crown eukaryote group genomes-was queried with a reference set of transcription-associated proteins (TAPs). Following clustering on the basis of sequence similarity of the TAPs with their homologs, and together with hidden Markov model profile searches, 156 P. falciparum TAPs were identified. This represents about a third of the number of TAPs usually found in the genome of a free-living eukaryote. Furthermore, the P. falciparum genome appears to contain a low number of sequences, which are highly conserved and abundant within the kingdoms of free-living eukaryotes, that contribute to gene-specific transcriptional regulation. However, in comparison with these other eukaryotic genomes, the CCCH-type zinc finger (common in proteins modulating mRNA decay and translation rates) was found to be the most abundant in the P. falciparum genome. This observation, together with the paucity of malarial transcriptional regulators identified, suggests Plasmodium protein levels are primarily determined by posttranscriptional mechanisms.

A Cluster of Ring Stage–specific Genes Linked to a Locus Implicated in Cytoadherence inPlasmodium falciparumCodes for PEXEL-negative and PEXEL-positive Proteins Exported into the Host Cell

“…However, it is possible that this gene encodes a protein for which the mRNA is stored and translated in a different life cycle stage or under certain conditions only. Discrepancies between transcription and translation in P. falciparum have been noted previously (Coulson et al, 2004). Alternatively, our sera might not be sensitive enough to detect REX4, which might be considerably less abundant than the transgenically expressed REX4 proteins.…”

An enhancer-like region regulates hrp3 promoter stage-specific gene expression in the human malaria parasite Plasmodium falciparum

“…The hrp3 enhancer region also contains a CCAAT at position -1487 bp to -1483 bp. This was not surprising since the parasite genome encodes the complete CCAAT-box binding complex [34]. However, CCAAT-box containing fragment A1 (Fig 2A and Fig.…”

A screen for conserved sequences with biased base composition identifies noncoding RNAs in the A–T rich genome of Plasmodium falciparum

“…Second, almost 15% of annotated genes show transcription of antisense RNAs in the asexual stages [7]. Finally, results from genomewide transcription analyses and bioinformatics studies show that compared to the yeast genome, the Plasmodium genome has an under-representation of DNA-binding proteins and transcription factors and over-representation of RNA-binding proteins [8] Recent data that compares transcriptome and proteome profiles in different stages of the parasite life cycle has revealed that post-transcriptional regulation via RNA-binding proteins may be a major mechanism of regulating gene expression in gametocytes and sexual stages [9]. These accumulating data suggest that there may be novel mechanisms of gene regulation in the malaria parasite, including mRNA stabilization, antisense RNA and ncRNA-mediated regulation.…”