Holmes et al. 2023 (PRJNA1017399)

General Details

Title Depletion of mRNA cap-binding protein eIF4E1 drives bradyzoite formation in Toxoplasma gondii [RIBO-seq]
Organism
Number of Samples 6
Release Date 2023/09/14 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP460544
ENA SRP460544
GEO
BioProject PRJNA1017399

Publication

Title
Authors Holmes MJ,Bastos MS,Dey V,Severo V,Wek RC,Sullivan WJ Jr
Journal bioRxiv : the preprint server for biology
Publication Date 2023 Oct 9
Abstract The protozoan parasite Toxoplasma gondii causes serious opportunistic disease due to its ability to persist in patients as latent tissue cysts. The molecular mechanisms coordinating conversion between proliferative parasites (tachyzoites) and dormant cysts (bradyzoites) are not fully understood. We previously showed that phosphorylation of eIF2α accompanies bradyzoite formation, suggesting that this clinically relevant process involves regulation of mRNA translation. In this study, we investigated the composition and role of eIF4F multi-subunit complexes in translational control. Using CLIPseq, we find that the cap-binding subunit, eIF4E1, localizes to the 5'-end of all tachyzoite mRNAs, many of which show evidence of stemming from heterogenous transcriptional start sites. We further show that eIF4E1 operates as the predominant cap-binding protein in two distinct eIF4F complexes. Using genetic and pharmacological approaches, we found that eIF4E1 deficiency triggers efficient spontaneous formation of bradyzoites without stress induction. Consistent with this result, we also show that stress-induced bradyzoites exhibit reduced eIF4E1 expression. Overall, our findings establish a novel role for eIF4F in translational control required for parasite latency and microbial persistence.
PMC PMC10592687
PMID 37873335
DOI
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)
SRR26060428 PRJNA1017399 Toxoplasma gondii RH::TIR1 parental straintachyzoites
SRR26060427 PRJNA1017399 Toxoplasma gondii RH::TIR1 parental straintachyzoites
SRR26060426 PRJNA1017399 Toxoplasma gondii RH::TIR1 parental straintachyzoites
SRR26060425 PRJNA1017399 Toxoplasma gondii RH::TIR1 parental straintachyzoites
SRR26060424 PRJNA1017399 Toxoplasma gondii RH::TIR1 parental straintachyzoites
SRR26060423 PRJNA1017399 Toxoplasma gondii RH::TIR1 parental straintachyzoites
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)

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