Cerox1 and microRNA-488-3p noncoding RNAs jointly regulate mitochondrial complex I catalytic activity
| Autor: | Ana C. Marques, Wilfried Haerty, Tamara Sirey, Nick Li, Chris P. Ponting, Kenny Roberts, Rogatti-Granados S, Cooper S, Jennifer Y. Tan, Oscar C. Bedoya-Reina, Lisa C. Heather |
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| Rok vydání: | 2018 |
| Předmět: |
0303 health sciences
Chemistry Protein subunit Cell Oxidative phosphorylation Genome Long non-coding RNA Cell biology 03 medical and health sciences 0302 clinical medicine medicine.anatomical_structure Cytoplasm microRNA medicine 030217 neurology & neurosurgery Function (biology) 030304 developmental biology |
| Popis: | To generate energy efficiently, the cell is uniquely challenged to co-ordinate the abundance of electron transport chain protein subunits expressed from both nuclear and mitochondrial genomes. How an effective stoichiometry of this many constituent subunits is co-ordinated post-transcriptionally remains poorly understood. Here we show that Cerox1, an unusually abundant cytoplasmic long noncoding RNA (lncRNA), modulates the levels of mitochondrial complex I subunit transcripts in a manner that requires binding to microRNA-488-3p. Increased abundance of Cerox1 cooperatively elevates complex I subunit protein abundance and enzymatic activity, decreases reactive oxygen species production, and protects against the complex I inhibitor rotenone. Cerox1 function is conserved across placental mammals: human and mouse orthologues effectively modulate complex I enzymatic activity in mouse and human cells, respectively. Cerox1 is the first lncRNA demonstrated, to our knowledge, to regulate mitochondrial oxidative phosphorylation (OXPHOS) and, with miR-488-3p, represent novel targets for the modulation of complex I activity. |
| Databáze: | OpenAIRE |
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