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Title

RNA-binding proteins regulate cell respiration and coenzyme Q biosynthesis by post-transcriptional regulation of COQ7

AuthorsCascajo Almenara, M. V. ; Fernández-Ayala, Daniel J. M.; Willers, Imke M. ; Brea-Calvo, Gloria ; López-Lluch, Guillermo ; Valenzuela-Villatoro, M.; Cuezva, José M. ; Siendones, Emilio ; Navas, Plácido
KeywordsHuR
Mitochondrial respiration
hnRNP C1/C2
Coenzyme Q10
COQ7
Post-transcriptional regulation
RNA-binding proteins
Issue Date2016
PublisherTaylor & Francis
CitationRNA Biology 13(7): 622-634 (2016)
AbstractCoenzyme Q (CoQ) is a key component of the mitochondrial respiratory chain carrying electrons from complexes I and II to complex III and it is an intrinsic component of the respirasome. CoQ concentration is highly regulated in cells in order to adapt the metabolism of the cell to challenges of nutrient availability and stress stimuli. At least 10 proteins have been shown to be required for CoQ biosynthesis in a multi-peptide complex and COQ7 is a central regulatory factor of this pathway. We found that the first 765 bp of the 3′-untranslated region (UTR) of COQ7 mRNA contains cis-acting elements of interaction with RNA-binding proteins (RBPs) HuR and hnRNP C1/C2. Binding of hnRNP C1/C2 to COQ7 mRNA was found to require the presence of HuR, and hnRNP C1/C2 silencing appeared to stabilize COQ7 mRNA modestly. By contrast, lowering HuR levels by silencing or depriving cells of serum destabilized and reduced the half-life of COQ7 mRNA, thereby reducing COQ7 protein and CoQ biosynthesis rate. Accordingly, HuR knockdown decreased oxygen consumption rate and mitochondrial production of ATP, and increased lactate levels. Taken together, our results indicate that a reduction in COQ7 mRNA levels by HuR depletion causes mitochondrial dysfunction and a switch toward an enhanced aerobic glycolysis, the characteristic phenotype exhibited by primary deficiency of CoQ. Thus HuR contributes to efficient oxidative phosphorylation by regulating of CoQ biosynthesis.
Descriptionet al.
Publisher version (URL)https://doi.org/10.1080/15476286.2015.1119366
URIhttp://hdl.handle.net/10261/163394
Identifiersdoi: 10.1080/15476286.2015.1119366
e-issn: 1555-8584
issn: 1547-6286
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