The long non-coding RNA Cerox1 is a post transcriptional regulator of mitochondrial complex I catalytic activity.

Journal article

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 and, with miR-488-3p, represent novel targets for the modulation of complex I activity.

Authors: Sirey, T; Roberts, K; Haerty, W; Bedoya-Reina, O; Rogatti-Granados, S

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: eLife Sciences Publications
• Journal: eLife
• Volume: 8
• Issue: 2019
• Article number: e45051
• Publication date: 2019-05-02
• Acceptance date: 2019-05-02
• DOI: 10.7554/eLife.45051
• ISSN: 2050-084X
• Pmid: 31045494
• Language: English
• Keywords: genetics; long noncoding RNA; chemical biology; miRNA; genomics; post-transcriptional regulation; energy metabolism; mitochondria; biochemistry