Alternative splicing of coq-2 controls the level of rhodoquinone in animals

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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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Article and author information

Author details

June H Tan

The Donnelly Centre, University of Toronto, Toronto, Canada

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-6597-3952
Margot Lautens

The Donnelly Centre, University of Toronto, Toronto, Canada

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The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-8503-9603
Laura Romanelli-Cedrez

Laboratorio de Biología de Gusanos. Unidad Mixta, Departamento de Biociencias, Facultad de Química, Universidad de la República, Institut Pasteur de Montevideo, Montevideo, Uruguay

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The authors declare that no competing interests exist.
Jianbin Wang

Dept. of Biochemistry & Cellular and Molecular Biology, The University of Tennessee, Knoxville, United States

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The authors declare that no competing interests exist.
Michael R Schertzberg

The Donnelly Centre, University of Toronto, Toronto, Canada

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The authors declare that no competing interests exist.
Samantha R Reinl

Department of Chemistry and Biochemistry, Gonzaga University, Spokane, United States

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Richard E Davis

Department of Biochemistry and Molecular Genetics, RNA Bioscience Initiative, University of Colorado School of Medicine, Aurora, United States

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The authors declare that no competing interests exist.
Jennifer N Shepherd

Department of Chemistry and Biochemistry, Gonzaga University, Spokane, United States

For correspondence
shepherd@gonzaga.edu

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The authors declare that no competing interests exist.
Andrew G Fraser

The Donnelly Centre, University of Toronto, Toronto, Canada

For correspondence
andyfraser.utoronto@gmail.com

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The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-9939-6014
Gustavo Salinas

Laboratorio de Biología de Gusanos. Unidad Mixta, Departamento de Biociencias, Facultad de Química, Universidad de la República, Institut Pasteur de Montevideo, Montevideo, Uruguay

For correspondence
gsalin@fq.edu.uy

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The authors declare that no competing interests exist.

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.

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