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| Status |
Public on Nov 02, 2023 |
| Title |
Depletion of mRNA cap-binding protein eIF4E1 drives bradyzoite formation in Toxoplasma gondii [CLIP-seq] |
| Organism |
Toxoplasma gondii |
| Experiment type |
Other
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| Summary |
Ingestion of Toxoplasma gondii results in life-long infection due to its ability to convert from the rapidly disseminating tachyzoite stage to the chronic, encysted bradyzoite stage. The control of mRNA translation has been suggested to play a key role in the signaling required to trigger bradyzoite formation. In eukaryotes, translational control primarily operates at two key points during the assembly of translation initiation factors. The phosphorylation of eIF2 affects mRNA start codon recognition and promotes differentiation in a variety of parasites. Modulating eIF4F function is the second pan-eukaryote regulatory point but remains unexplored in Toxoplasma. Here, we uncover the role that eIF4F-centric regulation plays in regulating bradyzoite formation by targeting the cap-binding subunit, eIF4E1. We discover that eIF4E1 coordinates two eIF4F complexes and binds the 5’-end of all mRNAs transcribed in tachyzoites, many of which show evidence of stemming from heterogenous transcriptional start sites. Together, this indicates that eIF4E1 is the predominant cap-binding protein in Toxoplasma tachyzoites. We also demonstrate that eIF4E1 knockdown or its chemical inhibition triggers the efficient formation of bradyzoites in the absence of other stresses and that stress-induced bradyzoites reduce their eIF4E1 expression. This study unearths a role for eIF4F-centric translational control in controlling Toxoplasma differentiation, suggesting that control of cap-dependent translation regulates the process of bradyzoite formation.
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| Overall design |
expression changes at the transcriptional and translational levels upon IAA-induced eIF4E1 depletion in Toxoplasma gondii tachyzoites
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| Contributor(s) |
Holmes MJ, Sullivan WJ Jr |
| Citation(s) |
38747593 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R21 AI167662 |
Regulation of cyst formation in the AIDS opportunistic pathogen Toxoplasma |
INDIANA UNIVERSITY |
William J Sullivan |
| R21 AI167662 |
Regulation of cyst formation in the AIDS opportunistic pathogen Toxoplasma |
INDIANA UNIVERSITY |
Ronald C Wek |
| R01 AI172752 |
Translation initiation factors driving persistence of Toxoplasma gondii bradyzoites in neurons |
INDIANA UNIVERSITY |
William J Sullivan |
| R01 AI172752 |
Translation initiation factors driving persistence of Toxoplasma gondii bradyzoites in neurons |
INDIANA UNIVERSITY |
Ronald C Wek |
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| Submission date |
Sep 14, 2023 |
| Last update date |
Jun 26, 2024 |
| Contact name |
Michael James Holmes |
| E-mail(s) |
holmesmi@iu.edu
|
| Organization name |
Indiana University School of Medicine
|
| Department |
Pharmacology & Toxicology
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| Street address |
635 Barnhill Drive
|
| City |
Indianapolis |
| State/province |
IN |
| ZIP/Postal code |
46202 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL23466 |
Illumina HiSeq 4000 (Toxoplasma gondii) |
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| Samples (12)
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| This SubSeries is part of SuperSeries: |
| GSE243207 |
Depletion of mRNA cap-binding protein eIF4E1 drives bradyzoite formation in Toxoplasma gondii |
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| Relations |
| BioProject |
PRJNA1017398 |
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