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Whole genome analysis of mRNA decay in P. falciparum reveals a lengthening of mRNA half-life during the IDC

ABSTRACT: The rate of mRNA decay is an essential element of post-transcriptional regulation in all organisms. Previously, studies in several organisms found that the specific half-life of each mRNA is precisely related to its physiological role, and plays an important role in determining levels of gene expression. We have used a genome wide approach to characterize mRNA decay in Plasmodium falciparum. We found that globally, rates of mRNA decay increase dramatically during the asexual intraerythrocytic developmental cycle. During the ring stage of the cycle, the average mRNA half-life was 9.5 minutes, yet this was extended to an average of 65 minutes during the late schizont stage of development. Thus a major determinant of mRNA decay rate appears to be linked to the stage of intraerythrocytic development. Furthermore, we have found specific variations in decay patterns superimposed upon the dominant trend of progressive half-life lengthening. These variations in decay pattern were frequently enriched for genes with specific cellular functions or processes. Elucidation of Plasmodium mRNA decay rates provides a key element for deciphering mechanisms of genetic control in this parasite, by complementing and extending previous mRNA abundance studies. Our results indicate that progressive stage-dependent decreases in mRNA decay rate function are a major determinant of mRNA accumulation during the schizont stage of intraerythrocytic development. This type of genome wide change in mRNA decay rate has not been observed in any other organism to date, and indicates that post-transcriptional regulation may be the dominant mechanism of gene regulation in P. falciparum. Keywords: Plasmodium falciparum treated with actinomycin D

ORGANISM(S): Saccharomyces cerevisiae Plasmodium falciparum

PROVIDER: GSE8099 | GEO | 2007/07/19

SECONDARY ACCESSION(S): PRJNA100955

REPOSITORIES: GEO

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Project description:Abstract of associated publication: Background: During the latter half of the natural 48-hour intraerythrocytic life cycle of human Plasmodium falciparum infection, parasites sequester deep in endothelium tissues, away from the spleen and inaccessible to peripheral blood. These late-stage parasites may cause tissue damage and likely contribute to clinical disease, and a more complete understanding of their biology is needed. Because these life cycle stages are not easily sampled due to deep tissue sequestration, measuring in vivo gene expression of parasites in the trophozoite and schizont stages has been a challenge. Methods: We developed a custom nCounter® gene expression platform, and used this platform to measure malaria parasite gene expression profiles in vitro and in vivo. We also used imputation to generate global transcriptional profiles, and assessed differential gene expression between parasites growing in vitro and those recovered from malaria-infected patient tissues collected at autopsy. Results: We demonstrate, for the first time, global transcriptional expression profiles from in vivo malaria parasites sequestered in human tissues. We found that parasite physiology can be correlated with in vitro data from an existing life cycle data set, and that parasites in sequestered tissues show an expected schizont-like transcriptional profile, which is conserved across tissues from the same patient. Imputation based on 60 landmark genes generated global transcriptional profiles that were highly correlated with genome-wide expression patterns from the same sample measured by microarray. Finally, differential expression revealed a limited set of in vivo upregulated transcripts, which may indicate unique parasite genes involved in human clinical infections. Conclusions: Our study highlights the utility of a custom nCounter® P. falciparum probe set, validation of imputation within Plasmodium species, and documentation of in vivo schizont-stage expression patterns from human tissues.

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Whole genome analysis of mRNA decay in P. falciparum reveals a lengthening of mRNA half-life during the IDC

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