RT Journal Article SR Electronic T1 Cerox1 and microRNA-488-3p noncoding RNAs jointly regulate mitochondrial complex I catalytic activity JF bioRxiv FD Cold Spring Harbor Laboratory SP 323907 DO 10.1101/323907 A1 Tamara M Sirey A1 Kenny Roberts A1 Wilfried Haerty A1 Oscar Bedoya-Reina A1 Sebastian Rogatti-Granados A1 Jennifer Y Tan A1 Nick Li A1 Lisa C Heather A1 Sarah Cooper A1 Ana C Marques A1 Chris P Ponting YR 2018 UL http://biorxiv.org/content/early/2018/05/16/323907.abstract AB 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.