The long non-coding rna cerox1 is a post transcriptional regulator of mitochondrial complex i catalytic activity

Sirey, Tamara M., Roberts, Kenny, Haerty, Wilfried, Bedoya-Reina, Oscar, Granados, Sebastian Rogatti, Tan, Jennifer Y., Li, Nick, Heather, Lisa C., Carter, Roderick N., Cooper, Sarah, Finch, Andrew J., Wills, Jimi, Morton, Nicholas M., Marques, Ana Claudia and Ponting, Chris P. (2019) The long non-coding rna cerox1 is a post transcriptional regulator of mitochondrial complex i catalytic activity. eLife, 8. ISSN 2050-084X

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Abstract

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.

Item Type: Article
Uncontrolled Keywords: neuroscience(all),immunology and microbiology(all),biochemistry, genetics and molecular biology(all) ,/dk/atira/pure/subjectarea/asjc/2800
Faculty \ School: Faculty of Science > School of Biological Sciences
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Depositing User: LivePure Connector
Date Deposited: 19 Feb 2021 01:04
Last Modified: 01 Aug 2021 00:09
URI: https://ueaeprints.uea.ac.uk/id/eprint/79282
DOI: 10.7554/eLife.45051

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