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

eLife

Michael R Schertzberg¹  Jianbin Wang²  Jennifer N Shepherd²  Richard E Davis³  Andrew G Fraser³  Laura Romanelli-Cedrez⁴  Margot Lautens⁵  June H Tan⁵  Samantha R Reinl⁵  Gustavo Salinas⁵ 

[1] Department of Biochemistry and Cellular and Molecular Biology, University of Tennessee, Knoxville, United States;Department of Biochemistry and Molecular Genetics, RNA Bioscience Initiative, University of Colorado School of Medicine, Aurora, United States;Department of Chemistry and Biochemistry, Gonzaga University, Spokane, United States;Laboratorio de Biología de Gusanos. Unidad Mixta, Departamento de Biociencias, Facultad de Química, Universidad de la República - Institut Pasteur de Montevideo, Montevideo, Uruguay;The Donnelly Centre, University of Toronto, Toronto, Canada;

关键词: rhodoquinone;    parasitic helminth;    anaerobic metabolism;    alternative splicing;    annelid;    mollusc;   

DOI  :  10.7554/eLife.56376

来源: DOAJ

【 摘 要 】

Parasitic helminths use two benzoquinones as electron carriers in the electron transport chain. In normoxia, they use ubiquinone (UQ), but in 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 of substrates by the polyprenyltransferase COQ-2 (Del Borrello et al., 2019; Roberts Buceta et al., 2019); however, the mechanism of substrate selection is not known. Here, we show helminths synthesize two coq-2 splice forms, coq-2a and coq-2e, and the coq-2e-specific exon is only found in species that synthesize RQ. We show that in Caenorhabditis elegans COQ-2e is required for efficient RQ synthesis and survival in cyanide. Importantly, parasites switch from COQ-2a to COQ-2e as they transit into anaerobic environments. We conclude helminths switch from UQ to RQ synthesis principally via changes in the alternative splicing of coq-2.

【 授权许可】

Unknown