Characterization of human malaria parasite Plasmodium falciparum eIF4E homologue and mRNA 5′ cap status

Shaw, Philip; Ponmee, Napawan; Karoonuthaisiri, Nitsara; Kamchonwongpaisan, Sumalee; Yuthavong, Yongyuth

doi:10.1016/j.molbiopara.2007.07.003

Cited by 26 publications

(22 citation statements)

References 36 publications

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“…Genomic DNA was removed from total RNA using a Turbo DNA free™ kit (Ambion, Applied Biosystems). The RNA was reverse-transcribed to cDNA using oligo-dT (21) primer, amino-allyl dUTP and ImpromII enzyme (Promega), and fluorescent cyanine dye coupled to amino-allyl labeled cDNA as described in [ 52 ]. cDNA from DHA or vehicle treated parasites was labeled with Cy5 and culture-matched control untreated parasite cDNA labeled with Cy3.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2015

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BackgroundControl 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. falciparum K1 strain and in P. berghei ANKA strain using microarray and RNA-seq technology.ResultsMicroarray data from DHA-treated P. falciparum trophozoite stage parasites revealed a response pattern that is overall less trophozoite-like and more like the other stages of asexual development. A meta-analysis of these data with previously published data from other ART treatments revealed a set of common differentially expressed genes. Notably, ribosomal protein genes are down-regulated in response to ART. A similar pattern of trophozoite transcriptomic change was observed from RNA-seq data. RNA-seq data from DHA-treated P. falciparum rings reveal a more muted response, although there is considerable overlap of differentially expressed genes with DHA-treated trophozoites. No genes are differentially expressed in DHA-treated P. falciparum schizonts. The transcriptional response of P. berghei to DHA treatment in vivo in infected mice is similar to the P. falciparum in vitro culture ring and trophozoite responses, in which ribosomal protein genes are notably down-regulated.ConclusionsRing and trophozoite stage Plasmodium respond to ART by arresting metabolic processes such as protein synthesis and glycolysis. This response can be protective in rings, as shown by the phenomenon of dormancy. In contrast, this response is not as protective in trophozoites owing to their commitment to a highly active and vulnerable metabolic state. The lower metabolic demands of schizonts could explain why they are less sensitive and unresponsive to ART. The ART response pattern is revealed clearly from RNA-seq data, suggesting that this technology is of great utility for studying drug response in Plasmodium.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-2040-0) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

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

et al. 2015

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“…Studies comparing transcriptional and translational profiles in the IDC reveal poor correlation and delay of up to 18 h in transcript and protein levels (Le Roch et al , ; Foth et al , , ; Bunnik et al , ), which suggests important roles for post‐transcriptional and translational regulation of gene expression in the IDC of P. falciparum (Vembar et al , ). Proposed mechanisms for post‐transcriptional control in P. falciparum include mRNA processing and degradation (Brengues et al , ; Newbury, ; Deitsch et al , ; Parker & Sheth, ; Sims et al , ; Yamasaki & Anderson, ; Horrocks et al , ), translational repression (Hall et al , ; Mair et al , ; Parker & Sheth, ; Shaw et al , ; Abaza & Gebauer, ), translational regulation by untranslated regions (UTR) in mRNA (Hasenkamp et al , ; Brancucci et al , ; Cui et al , ), and natural (endogenous) anti‐sense transcripts (Patankar et al , ; Kyes et al , ; Gunasekera et al , ; Militello et al , , ; Lu et al , ). However, these gene‐specific mechanisms which have local effects do not explain a more global systematic scale mechanism involved in the control of Plasmodium gene expression at the level of translation.…”

Section: Introductionmentioning

confidence: 99%

tRNA epitranscriptomics and biased codon are linked to proteome expression in Plasmodium falciparum

Sinha

Aniweh

et al. 2018

Molecular Systems Biology

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Among components of the translational machinery, ribonucleoside modifications on tRNAs are emerging as critical regulators of cell physiology and stress response. Here, we demonstrate highly coordinated behavior of the repertoire of tRNA modifications of Plasmodium falciparum throughout the intra‐erythrocytic developmental cycle (IDC). We observed both a synchronized increase in 22 of 28 modifications from ring to trophozoite stage, consistent with tRNA maturation during translational up‐regulation, and asynchronous changes in six modifications. Quantitative analysis of ~2,100 proteins across the IDC revealed that up‐ and down‐regulated proteins in late but not early stages have a marked codon bias that directly correlates with parallel changes in tRNA modifications and enhanced translational efficiency. We thus propose a model in which tRNA modifications modulate the abundance of stage‐specific proteins by enhancing translation efficiency of codon‐biased transcripts for critical genes. These findings reveal novel epitranscriptomic and translational control mechanisms in the development and pathogenesis of Plasmodium parasites.

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“…The raw intensity data from both channels were pre-processed as described previously in [22], and normalized within arrays using the global lowess algorithm and across replicate arrays from the same experiment in the Aroma package [23] run in R 2.8.1 project environment [24]. All microarray data and details of experimental design were submitted to the NCBI Gene Expression Omnibus (GEO) database and are available under series accession numbers GSE31109, GSE30867 and GSE30869.…”

Section: Methodsmentioning

confidence: 99%

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

Kritsiriwuthinan

Chaotheing

Shaw

et al. 2011

Malar J

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BackgroundPyronaridine (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.MethodsSynchronized trophozoite stage cultures of P. falciparum strain K1 (CQ resistant) were exposed to 50% inhibitory concentrations (IC50) of PN and CQ, and parasites were harvested from culture after 4 and 24 hours exposure. Global transcriptional changes effected by drug treatment were investigated using DNA microarrays.ResultsAfter a 4 h drug exposure, PN induced a greater degree of transcriptional perturbation (61 differentially expressed features) than CQ (10 features). More genes were found to respond to 24 h treatments with both drugs, and 461 features were found to be significantly responsive to one or both drugs across all treatment conditions.Filtering was employed to remove features unrelated to primary drug action, specifically features representing genes developmentally regulated, secondary stress/death related processes and sexual stage development. The only significant gene ontologies represented among the 46 remaining features after filtering relate to host exported proteins from multi-gene families.ConclusionsThe malaria parasite's molecular responses to PN and CQ treatment are similar in terms of the genes and pathways affected. However, PN appears to exert a more rapid response than CQ. The faster action of PN may explain why PN is more efficacious than CQ, particularly against CQ resistant isolates. In agreement with several other microarray studies of drug action on the parasite, it is not possible, however, to discern mechanism of drug action from the drug-responsive genes.

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Characterization of human malaria parasite Plasmodium falciparum eIF4E homologue and mRNA 5′ cap status

Cited by 26 publications

References 36 publications

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

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

tRNA epitranscriptomics and biased codon are linked to proteome expression in Plasmodium falciparum

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

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