Transcriptomic complexity of the human malaria parasite Plasmodium falciparum revealed by long-read sequencing.

The Plasmodium falciparum human malaria parasite genome is incompletely annotated and does not accurately represent the transcriptomic diversity of this species. To address this need, we performed long-read transcriptomic sequencing. 5' capped mRNA was enriched from samples of total and nuclear-fractionated RNA from intra-erythrocytic stages and converted to cDNA library.

Investigation of an Allosteric Deoxyhypusine Synthase Inhibitor in .

The treatment of a variety of protozoal infections, in particular those causing disabling human diseases, is still hampered by a lack of drugs or increasing resistance to registered drugs. However, in recent years, remarkable progress has been achieved to combat neglected tropical diseases by sequencing the parasites’ genomes or the validation of new targets in the parasites by novel genetic manipulation techniques, leading to loss of function. The novel amino acid hypusine is a posttranslational modification (PTM) that occurs in eukaryotic initiation factor 5A (EIF5A) at a specific lysine residue.

Identification of mRNA 5' cap-associated proteins in the human malaria parasite Plasmodium falciparum.

Eukaryotic messenger RNA is translated via a 5' cap-dependent initiation mechanism. Experimental evidence for proteins involved with translation initiation among eukaryotic parasites is lacking, including Plasmodium falciparum, the human malaria parasite. Native P.

Identifying transcript 5' capped ends in .

Background: The genome of the human malaria parasite is poorly annotated, in particular, the 5' capped ends of its mRNA transcripts. New approaches are needed to fully catalog transcripts for understanding gene function and regulation in this organism.

Methods: We developed a transcriptomic method based on next-generation sequencing of complementary DNA (cDNA) enriched for full-length fragments using eIF4E, a 5' cap-binding protein, and an unenriched control.

Hybrid Inhibitors of Malarial Dihydrofolate Reductase with Dual Binding Modes That Can Forestall Resistance.

The S108N mutation of dihydrofolate reductase (DHFR) renders malaria parasites resistant to pyrimethamine through steric clash with the rigid side chain of the inhibitor. Inhibitors with flexible side chains can avoid this clash and retain effectiveness against the mutant. However, other mutations such as N108S reversion confer resistance to flexible inhibitors.

Estimating mRNA lengths from Plasmodium falciparum genes by Virtual Northern RNA-seq analysis.

Accurate gene models are essential for understanding parasite biology. However, transcript structure information is lacking for most parasite genes. Here, we describe "Virtual Northern" analysis of the malaria parasite Plasmodium falciparum to address this issue.

Plasmodium parasites mount an arrest response to dihydroartemisinin, as revealed by whole transcriptome shotgun sequencing (RNA-seq) and microarray study.

Background: Control of malaria is threatened by emerging parasite resistance to artemisinin and derivative drug (ART) therapies. The molecular detail of how Plasmodium malaria parasites respond to ART and how this could contribute to resistance are not well understood. To address this question, we performed a transcriptomic study of dihydroartemisinin (DHA) response in P.

Molecular characterization of Plasmodium falciparum Bruno/CELF RNA binding proteins.

The human malaria parasite Plasmodium falciparum employs intricate post-transcriptional regulatory mechanisms in different stages of its life cycle. Despite the importance of post-transcriptional regulation, key elements of these processes, namely RNA binding proteins (RBPs), are poorly characterized. In this study, the RNA binding properties of P.

Inducible knockdown of Plasmodium gene expression using the glmS ribozyme.

Conventional reverse genetic approaches for study of Plasmodium malaria parasite gene function are limited, or not applicable. Hence, new inducible systems are needed. Here we describe a method to control P.

Global gene expression profiling of Plasmodium falciparum in response to the anti-malarial drug pyronaridine.

Background: Pyronaridine (PN) and chloroquine (CQ) are structurally related anti-malarial drugs with primarily the same mode of action. However, PN is effective against several multidrug-resistant lines of Plasmodium falciparum, including CQ resistant lines, suggestive of important operational differences between the two drugs.

Methods: Synchronized trophozoite stage cultures of P.