Characterization of the BFD2-bound transcriptome in chronic-stage T. gondii
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA926983 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR23205003_1.fastq.gz | Fastqsanger.gz | |||
| SRR23205003_2.fastq.gz | Fastqsanger.gz | |||
| SRR23205004_1.fastq.gz | Fastqsanger.gz | |||
| SRR23205004_2.fastq.gz | Fastqsanger.gz |
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Project description:The acute-to-chronic stage transition in Toxoplasma gondii involes a global restructuring of the parasite transcriptome and can be induced by alkaline stress. Prior work identified the master regulator of this process: a MYB-like transcription factor named BFD1 that is specifically induced under stress and is both necessary and sufficient to drive differentiation. Recently, we found that parasites lacking a CCCH-type zinc finger RNA-binding protein (BFD2) are also unable to produce chronic forms due to an inability to robustly express BFD1. To test whether the influence of BFD2 on BFD1 expression involves interaction with this or other transcripts, we performed BFD2 immunoprecipitation and sequencing (RIP-seq) under alkaline stress.
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Project description:Toxoplasma gondii persists in humans by converting from actively replicating acute stage tachyzoites to slow-growing chronic stage bradyzoites. The molecular mechanisms that mediate T. gondii differentiation remain poorly understood. Through a chemical mutagenesis screen, we identified translation initiation factor eIF1.2 as being critical for T. gondii differentiation. The presence of an F97L mutation in eIF1.2 identified in the screen or the complete lack eIF1.2 (∆eIF1.2) markedly impeded bradyzoite cyst formation in culture and in the brains of infected mice. ∆eIF1.2 parasites were defective in the upregulation of bradyzoite differentiation regulators BFD1 and BFD2 during stress-induced differentiation. Conditional overexpression of BFD1 or BFD2 rescued differentiation in ∆eIF1.2 parasites. We further show that eiF1.2 interacted with the yeast 40S ribosome and directed the scanning of a model 5’ untranslated region. Together, our findings imply that eIF1.2 functions by regulating the translation of key differentiation factors necessary to establish T. gondii chronic infection.
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Project description:The acute-to-chronic stage transition in Toxoplasma gondii involes a global restructuring of the parasite transcriptome and is induced under alkaline stress. We found that parasites lacking the RNA-binding protein BFD2 are unable to produce chronic forms, consistent with a block in this develomental program. To understand how BFD2 facilitates chronic-stage transcriptional reprogramming in T. gondii, we profiled the transcriptomes of both 'wildtype' and BFD2-knockout parasites under alkaline-stressed and standard culture conditions
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Project description:The protozoan pathogen Toxoplasma gondii has the unique ability to develop a chronic infection in the brain of its host. The T. gondii develops cysts within the neurons that are resilient against the host immune response and current therapeutics. The bradyzoite parasites within the cyst have a sugar-protein-rich wall and a slow-replication cycle, allowing them to remain hidden from the host. This intracellular encysted lifestyle of T. gondii has made them recalcitrant to molecular analysis in vivo. Here, we have enriched for T. gondii brain cysts 21 to 150 days post-infection (DPI). RNA and protein from bradyzoites was isolated from each timepoint. Deep sequencing of transcripts expressed during these three timepoints showed many of the identified proteins are transcriptionally expressed at a high level. Approximately one-third are more enriched during bradyzoite conditions compared to tachyzoites, and approximately half are expressed at similar levels during each phase. We have expanded the transcriptional profile of in vivo bradyzoites to 120 DPI. The RNA sequencing depth of in vivo bradyzoite T. gondii was over 250-fold greater than was have been previously, which allowed us to identify low level transcripts and novel bradyzoite-specific isoforms.
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Project description:Differentiation of proliferative acute stages into semi-quiescent chronic stages is key for Toxoplasma gondii persistence within an infected host. During natural infection, chronic stages are almost exclusively found in neurons, and it is well appreciated that neurons support high rates of spontaneous differentiation in cell culture. Recently, we found that parasites lacking the RNA-binding protein BFD2 are unable to produce chronic forms, consistent with a block in this develomental program. To compare the effects of BFD1 and BFD2 on chronic-stage transcriptional reprogramming in T. gondii, we profiled the transcriptomes of both 'wildtype' and BFD1- and BFD2-knockout parasites during infection of murine primary neurons.
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