RNA-binding proteins regulate cell respiration and coenzyme Q biosynthesis by post-transcriptional regulation of COQ7
| Autor: | Myriam Gorospe, Guillermo López-Lluch, Marina Valenzuela-Villatoro, Ji Heon Noh, Daniel J. M. Fernández-Ayala, Imke M. Willers, Emilio Siendones, Gloria Brea, José M. Cuezva, Kotb Abdelmohsen, Plácido Navas, María V. Cascajo |
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| Přispěvatelé: | Ministerio de Economía y Competitividad (España), Instituto de Salud Carlos III, National Institutes of Health (US), Ministerio de Sanidad, Servicios Sociales e Igualdad (España) |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Untranslated region Ubiquinone RNA-binding protein RNA-binding proteins Oxidative phosphorylation COQ7 Biology Oxidative Phosphorylation ELAV-Like Protein 1 03 medical and health sciences Oxygen Consumption coenzyme Q10 mitochondrial respiration Humans Molecular Biology 3' Untranslated Regions Gene knockdown 030102 biochemistry & molecular biology Post-transcriptional regulation Heterogeneous-Nuclear Ribonucleoprotein Group C Cell Biology 030104 developmental biology Mitochondrial respiratory chain Biochemistry Gene Expression Regulation Coenzyme Q – cytochrome c reductase Respirasome HuR Coenzyme Q10 hnRNP C1/C2 Research Article Research Paper post-transcriptional regulation HeLa Cells Mitochondrial respiration |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname RNA Biology article-version (VoR) Version of Record |
| Popis: | et al. Coenzyme 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. This research was supported by grants from the Spanish Ministry of Health, Instituto de Salud Carlos III (ISCIII), FIS PI14–01962 to PN, the Spanish Ministry of Economy and Competitively, SAF2013–41945-R to JMC, and the Intramural Research Program of the NIA, NIH (KA, MG). |
| Databáze: | OpenAIRE |
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