Alternative splicing of COQ-2 determines the choice between ubiquinone and rhodoquinone biosynthesis in helminths
| Autor: | Jennifer N. Shepherd, Andrew G. Fraser, Gustavo Salinas, Michael R Schertzberg, Richard E. Davis, Jianbin Wang, Laura Romanelli-Cedrez, Margot Lautens, Samantha R. Reinl, June H. Tan |
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| Rok vydání: | 2020 |
| Předmět: |
chemistry.chemical_classification
0303 health sciences Rhodoquinone Alternative splicing food and beverages Electron transport chain 03 medical and health sciences Exon chemistry.chemical_compound 0302 clinical medicine Enzyme chemistry Biosynthesis Biochemistry Helminths Anaerobic exercise 030217 neurology & neurosurgery 030304 developmental biology |
| Popis: | Parasitic helminths use two benzoquinones as electron carriers in the electron transport chain. In aerobic environments they use ubiquinone (UQ) but in anaerobic environments inside the host, they require rhodoquinone (RQ) and greatly increase RQ levels. The switch to RQ synthesis is driven by substrate selection by the polyprenyltransferase COQ-2 but the mechanisms underlying this substrate choice are unknown. We found that helminths make twocoq-2isoforms,coq-2aandcoq-2e, by alternative splicing. COQ-2a is homologous to COQ2 from other eukaryotes but the COQ-2e-specific exon is only found in species that make RQ and its inclusion changes the enzyme core. We show COQ-2e is required for RQ synthesis and for survival in cyanide inC. elegans. Crucially, we see a switch from COQ-2a to COQ-2e as parasites transition into anaerobic environments. We conclude that under anaerobic conditions helminths switch from UQ to RQ synthesis via alternative splicing ofcoq-2. |
| Databáze: | OpenAIRE |
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