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Published on: May 16, 2013
Mediator Complex of the Malaria Parasite Plasmodium falciparum Associates with Evolutionarily Novel Subunits
Uthra Balasubramaniyan Iyer1, Jung Eun Park1, Siu Kwan Sze1
1School of Biological Sciences, Nanyang Technological University, 50 Nanyang Avenue, Singapore 637551, Singapore.
Abstract:
The eukaryotic Mediator is a large and conserved multisubunit protein complex that directly contacts RNA polymerase II and impinges on multiple aspects of gene expression. The genome of the human malaria parasite Plasmodium falciparum has been predicted to encode several Mediator subunits. We provide physical evidence for the presence of a Mediator complex in P. falciparum by using coimmunoprecipitation and mass spectrometry to identify interaction partners of the highly conserved Mediator subunit PfMed31. We identify 11 of 14 predicted Mediator subunits and the products of two uncharacterized genes, PF3D7_0526800 and PF3D7_1363600, which are strongly associated with PfMed31. As expected, several additional interaction partners have known roles in the transcriptional control of gene expression and mRNA processing. Intriguingly, multiple interaction partners are implicated in endoplasmic reticulum function and the ER stress (ERS) response, suggesting crosstalk between the ERS response and the transcriptional machinery. Our results establish for the first time the physical presence of the Mediator complex within P. falciparum and strongly suggest that it plays both conserved and unique roles in the control of gene expression. Data are available via ProteomeXchange with the identifier PXD027640.
Insights
Researchers found physical evidence of the Mediator complex in the malaria parasite Plasmodium falciparum. This discovery reveals its role in gene expression and potential links to endoplasmic reticulum stress responses.
Area of Science:
- Molecular Biology
- Parasitology
- Genetics
Background:
- The Mediator complex is a crucial regulator of gene expression in eukaryotes, interacting with RNA polymerase II.
- The genome of Plasmodium falciparum, the human malaria parasite, was predicted to contain several Mediator subunits.
- Understanding gene regulation in P. falciparum is vital for developing new antimalarial strategies.
Purpose of the Study:
- To provide physical evidence for the existence of a Mediator complex in Plasmodium falciparum.
- To identify the subunits and interaction partners of the Mediator complex in P. falciparum.
- To explore the potential roles of the Mediator complex in P. falciparum gene expression and cellular processes.
Main Methods:
- Co-immunoprecipitation was used to isolate proteins interacting with the PfMed31 subunit.
- Mass spectrometry was employed to identify the co-immunoprecipitated proteins.
- Bioinformatic analysis was used to identify predicted Mediator subunits in the P. falciparum genome.
Main Results:
- Physical evidence for the Mediator complex in P. falciparum was established.
- Eleven of fourteen predicted Mediator subunits were identified, along with two uncharacterized proteins (PF3D7_0526800 and PF3D7_1363600).
- Interaction partners involved in transcriptional control, mRNA processing, and endoplasmic reticulum (ER) function/stress response were identified, suggesting crosstalk.
Conclusions:
- The Mediator complex is physically present in Plasmodium falciparum.
- The complex plays both conserved and unique roles in regulating gene expression.
- The identified crosstalk between the Mediator complex and ER stress response pathways offers new avenues for research.
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