The nematode homologue of Mediator complex subunit 28, F28F8.5, is a critical regulator ofC. elegansdevelopment

Author:

Kostrouchová Markéta12,Kostrouch David1,Chughtai Ahmed A.1ORCID,Kaššák Filip1,Novotný Jan P.1ORCID,Kostrouchová Veronika1,Benda Aleš3,Krause Michael W.4,Saudek Vladimír5,Kostrouchová Marta1,Kostrouch Zdeněk1

Affiliation:

1. Biocev, First Faculty of Medicine, Charles University, Prague, Czech Republic

2. Department of Pathology, Third Faculty of Medicine, Charles University, Prague, Czech Republic

3. Imaging Methods Core Facility, BIOCEV, Faculty of Science, Charles University, Prague, Czech Republic

4. Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA

5. Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, UK

Abstract

The evolutionarily conserved Mediator complex is a critical player in regulating transcription. Comprised of approximately two dozen proteins, the Mediator integrates diverse regulatory signals through direct protein-protein interactions that, in turn, modulate the influence of Mediator on RNA Polymerase II activity. One Mediator subunit, MED28, is known to interact with cytoplasmic structural proteins, providing a potential direct link between cytoplasmic dynamics and the control of gene transcription. Although identified in many animals and plants, MED28 is not present in yeast; no bona fide MED28 has been described previously inCaenorhabditis elegans.Here, we identify bioinformatically F28F8.5, an uncharacterized predicted protein, as the nematode homologue of MED28. As in other Metazoa, F28F8.5 has dual nuclear and cytoplasmic localization and plays critical roles in the regulation of development.F28F8.5is a vital gene and its null mutants have severely malformed gonads and do not reproduce. F28F8.5 interacts on the protein level with the Mediator subunits MDT-6 and MDT-30. Our results indicate that F28F8.5 is an orthologue of MED28 and suggest that the potential to link cytoplasmic and nuclear events is conserved between MED28 vertebrate and nematode orthologues.

Funder

European Regional Development Fund “BIOCEV—Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University in Vestec”

The Start-Up Grant

Ministry of Education, Youth and Sports of Czech Republic

Charles University in Prague

European Fund for Regional Development

Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health, USA

MediCentrum Praha, Czech Republic

Czech-BioImaging large RI project (MEYS CR)

Publisher

PeerJ

Subject

General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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