Mediator complex of the malaria parasite plasmodium falciparum associates with evolutionarily novel subunits

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 provid...

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Main Authors: Iyer, Uthra Balasubramaniyan, Park, Jung Eun, Sze, Siu Kwan, Bozdech, Zbynek, Featherstone, Mark
Other Authors: School of Biological Sciences
Format: Article
Language:English
Published: 2022
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Online Access:https://hdl.handle.net/10356/161016
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spelling sg-ntu-dr.10356-1610162023-02-28T17:13:15Z Mediator complex of the malaria parasite plasmodium falciparum associates with evolutionarily novel subunits Iyer, Uthra Balasubramaniyan Park, Jung Eun Sze, Siu Kwan Bozdech, Zbynek Featherstone, Mark School of Biological Sciences Science::Biological sciences Parasites Biopolymers 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. Ministry of Education (MOE) National Medical Research Council (NMRC) Published version This work was supported by a grant from the Singapore National Medical Research Council (NMRC) (#CBRG12nov104) to M.F. and L.W., the NMRC (NMRC/ OFIRG/0003/2016) to S.K.S., and the AcRF Tier 2 grant from the Singapore Ministry of Education [#MOE2017-T2-2- 030 (S)] to Z.B. 2022-08-11T07:48:12Z 2022-08-11T07:48:12Z 2022 Journal Article Iyer, U. B., Park, J. E., Sze, S. K., Bozdech, Z. & Featherstone, M. (2022). Mediator complex of the malaria parasite plasmodium falciparum associates with evolutionarily novel subunits. ACS Omega, 7(17), 14867-14874. https://dx.doi.org/10.1021/acsomega.2c00368 2470-1343 https://hdl.handle.net/10356/161016 10.1021/acsomega.2c00368 35557691 2-s2.0-85129558801 17 7 14867 14874 en CBRG12nov104 NMRC/OFIRG/0003/2016 MOE2017-T2-2-030 (S) ACS Omega © 2022 The Authors. Published by American Chemical Society. This is an open-access article distributed under the terms of the Creative Commons Attribution License. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Biological sciences
Parasites
Biopolymers
spellingShingle Science::Biological sciences
Parasites
Biopolymers
Iyer, Uthra Balasubramaniyan
Park, Jung Eun
Sze, Siu Kwan
Bozdech, Zbynek
Featherstone, Mark
Mediator complex of the malaria parasite plasmodium falciparum associates with evolutionarily novel subunits
description 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.
author2 School of Biological Sciences
author_facet School of Biological Sciences
Iyer, Uthra Balasubramaniyan
Park, Jung Eun
Sze, Siu Kwan
Bozdech, Zbynek
Featherstone, Mark
format Article
author Iyer, Uthra Balasubramaniyan
Park, Jung Eun
Sze, Siu Kwan
Bozdech, Zbynek
Featherstone, Mark
author_sort Iyer, Uthra Balasubramaniyan
title Mediator complex of the malaria parasite plasmodium falciparum associates with evolutionarily novel subunits
title_short Mediator complex of the malaria parasite plasmodium falciparum associates with evolutionarily novel subunits
title_full Mediator complex of the malaria parasite plasmodium falciparum associates with evolutionarily novel subunits
title_fullStr Mediator complex of the malaria parasite plasmodium falciparum associates with evolutionarily novel subunits
title_full_unstemmed Mediator complex of the malaria parasite plasmodium falciparum associates with evolutionarily novel subunits
title_sort mediator complex of the malaria parasite plasmodium falciparum associates with evolutionarily novel subunits
publishDate 2022
url https://hdl.handle.net/10356/161016
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