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| Status |
Public on Mar 26, 2024 |
| Title |
Timecourse of transcriptional changes upon eIF4E1 depletion in Toxoplasma gondii |
| Organism |
Toxoplasma gondii |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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 latent 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.
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| Overall design |
Expression changes in Toxoplasma upon IAA-induced knockdown of eIF4E1mAID for 24h and 48h in RH and ME49 strain backgrounds
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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 |
Mar 22, 2024 |
| Last update date |
Jun 26, 2024 |
| Contact name |
Michael James Holmes |
| E-mail(s) |
[email protected]
|
| Organization name |
Indiana University School of Medicine
|
| Department |
Pharmacology & Toxicology
|
| Street address |
635 Barnhill Drive
|
| City |
Indianapolis |
| State/province |
IN |
| ZIP/Postal code |
46202 |
| Country |
USA |
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| Platforms (1) |
| GPL26742 |
Illumina NovaSeq 6000 (Toxoplasma gondii) |
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| Samples (18)
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| Relations |
| BioProject |
PRJNA1090882 |
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