• Media type: E-Article
  • Title: The long non-coding RNA Cerox1 is a post transcriptional regulator of mitochondrial complex I catalytic activity
  • Contributor: Sirey, Tamara M; Roberts, Kenny; Haerty, Wilfried; Bedoya-Reina, Oscar; Rogatti-Granados, Sebastian; Tan, Jennifer Y; Li, Nick; Heather, Lisa C; Carter, Roderick N; Cooper, Sarah; Finch, Andrew J; Wills, Jimi; Morton, Nicholas M; Marques, Ana Claudia; Ponting, Chris P
  • Published: eLife Sciences Publications, Ltd, 2019
  • Published in: eLife, 8 (2019)
  • Language: English
  • DOI: 10.7554/elife.45051
  • ISSN: 2050-084X
  • Origination:
  • Footnote:
  • Description: 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.
  • Access State: Open Access