Cerox1 and microRNA-488-3p noncoding RNAs jointly regulate mitochondrial complex I catalytic activity

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.

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Author Sirey, Tamara M
Last Updated November 20, 2019, 16:48 (UTC)
Created August 1, 2019, 10:29 (UTC)
Article Host Type publisher
Article Is Open Access true
Article License Type cc-by-nc-nd
Article Version Type publishedVersion
Citation Report https://scite.ai/reports/10.1101/323907
DOI 10.1101/323907
Date Last Updated 2019-03-25T18:41:49.188284
Evidence open (via page says license)
Funder code(s)
Journal Is Open Access false
Open Access Status hybrid
PDF URL https://www.biorxiv.org/content/biorxiv/early/2018/05/16/323907.full.pdf
Publisher URL https://doi.org/10.1101/323907