Abstract
BackgroundThe lytic cycle of the protozoan parasite Toxoplasma gondii, which involves a brief sojourn in the extracellular space, is characterized by defined transcriptional profiles. For an obligate intracellular parasite that is shielded from the cytosolic host immune factors by a parasitophorous vacuole, the brief entry into the extracellular space is likely to exert enormous stress. Due to its role in cellular stress response, we hypothesize that translational control plays an important role in regulating gene expression in Toxoplasma during the lytic cycle. Unlike transcriptional profiles, insights into genome-wide translational profiles of Toxoplasma gondii are lacking.MethodsWe have performed genome-wide ribosome profiling, coupled with high throughput RNA sequencing, in intracellular and extracellular Toxoplasma gondii parasites to investigate translational control during the lytic cycle.ResultsAlthough differences in transcript abundance were mostly mirrored at the translational level, we observed significant differences in the abundance of ribosome footprints between the two parasite stages. Furthermore, our data suggest that mRNA translation in the parasite is potentially regulated by mRNA secondary structure and upstream open reading frames.ConclusionWe show that most of the Toxoplasma genes that are dysregulated during the lytic cycle are translationally regulated.
Highlights
The lytic cycle of the protozoan parasite Toxoplasma gondii, which involves a brief sojourn in the extracellular space, is characterized by defined transcriptional profiles
The basic concept of ribosome profiling is that actively translated mRNAs are protected from ribonucleases by the decoding ribosomes
Using a Benjamini-Hochberg False Discovery Rate (FDR) ≤ 10%, we identified three classes of differentially regulated genes: 1) 891 genes that varied both at the level of transcript abundance and ribosome occupancy i.e. concordant (RNA + RIBO) (Additional file 2 D), 2) 645 genes that varied only at the levels of mRNA abundance (RNA-ONLY) (Additional file 2 E), and 3) 1324 genes that varied only at the level of ribosome occupancy (RIBO-ONLY) (Fig. 3a and Additional file 2 F), indicating that many of the genes that are dysregulated in Toxoplasma during the lytic cycle are regulated at the translational level
Summary
The lytic cycle of the protozoan parasite Toxoplasma gondii, which involves a brief sojourn in the extracellular space, is characterized by defined transcriptional profiles. For an obligate intracellular parasite that is shielded from the cytosolic host immune factors by a parasitophorous vacuole, the brief entry into the extracellular space is likely to exert enormous stress. Due to its role in cellular stress response, we hypothesize that translational control plays an important role in regulating gene expression in Toxoplasma during the lytic cycle. During the lytic cycle the parasite invades a host cell, replicates, and lyses out of the host cell before infecting a new host cell. This process temporarily exposes the parasite to the extracellular milieu. Regulating transcript abundance, and by extension their protein products, is key in regulating Toxoplasma developmental stages and intercellular transmission
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