2020
DOI: 10.7554/elife.56376
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Alternative splicing of coq-2 controls the levels of rhodoquinone in animals

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-… Show more

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Cited by 18 publications
(38 citation statements)
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“…CC-BY 4.0 International license available under a (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made animals make an unusual splice form (COQ-2e in C.elegans) that includes the STH-specific residues (Tan et al, 2020), but did not confirm the functional importance of these two amino acids for RQ-synthesis. Here, we used CRISPR genome engineering to change these two residues in the COQ-2a isoform.…”
Section: Functional Significance Of Sth-specific Residuesmentioning
confidence: 92%
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“…CC-BY 4.0 International license available under a (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made animals make an unusual splice form (COQ-2e in C.elegans) that includes the STH-specific residues (Tan et al, 2020), but did not confirm the functional importance of these two amino acids for RQ-synthesis. Here, we used CRISPR genome engineering to change these two residues in the COQ-2a isoform.…”
Section: Functional Significance Of Sth-specific Residuesmentioning
confidence: 92%
“…A crucial early step in synthesis of these distinct quinones is the prenylation of either of these two precursors by the polyprenyltransferase COQ-2 -the substrate choice by COQ-2 is the key event that dictates whether UQ or RQ will be synthesised (Tan et al, 2020). We recently found that the choice of substrate for COQ-2 is determined by a single alternative splicing event which changes the enzyme core from a conserved 4HB-utilizing enzyme to a helminth-specific 3HA-preferring enzyme (Tan et al, 2020). The splice variant that uses 3HA as its preferred substrate has two helminth-specific residues deep in its active site making it an attractive drug target since it should be possible to identify inhibitors that specifically inhibit this RQ-synthesising form.…”
Section: Multiple Enzymes Required For Rq Synthesis Have Helminth-spementioning
confidence: 99%
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