Alternative splicing of coq-2 controls the level of rhodoquinone in animals
- University of Toronto, Canada
- Institut Pasteur de Montevideo, Uruguay
- The University of Tennessee, United States
- Gonzaga University, United States
- University of Colorado School of Medicine, United States
Abstract
Parasitic helminths use two benzoquinones as electron carriers in the electron transport chain. In normoxia they use ubiquinone (UQ), but in the anaerobic conditions inside the host, they require rhodoquinone (RQ) and greatly increase RQ levels. We previously showed the switch from UQ to RQ synthesis is driven by a change in substrates by the polyprenyltransferase COQ-2 (Del Borrello et al., 2019; Roberts Buceta et al., 2019) - how this substrate choice is made is unknown. Here, we show helminths make two coq-2 splice forms, coq-2a and coq-2e, and the coq-2e-specific exon is only found in species that make RQ. We show that in C. elegans COQ-2e is required for efficient RQ synthesis and for survival in cyanide. Crucially, parasites switch from COQ-2a to COQ-2e as they transition into anaerobic environments. We conclude helminths switch from UQ to RQ synthesis principally via changes in the alternative splicing of coq-2.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
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Author details
Funding
Canadian Institutes of Health Research (501584)
- Andrew G Fraser
Canadian Institutes of Health Research (5003009)
- Andrew G Fraser
Agencia Nacional de Investigación e Innovación (FCE_2014_1_104366)
- Gustavo Salinas
Agencia Nacional de Investigación e Innovación (FCE_1_2019_1_155779)
- Gustavo Salinas
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2020, Tan et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Alternative splicing of coq-2 controls the level of rhodoquinone in animals
eLife 9:e56376.
https://doi.org/10.7554/eLife.56376
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