The long non-coding RNA Cerox1 is a post transcriptional regulator of mitochondrial complex I catalytic activity
- University of Edinburgh, United Kingdom
- University of Oxford, United Kingdom
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.
Data availability
Microarray data are available through ArrayExpress, accession code E-MATB-6792
Article and author information
Author details
Ana Claudia Marques
Funding
Wellcome (WT106956/Z/15/Z)
- Tamara M Sirey
- Oscar Bedoya-Reina
- Sebastian Rogatti-Granados
- Chris P Ponting
European Research Council (249869)
- Tamara M Sirey
- Kenny Roberts
- Ana Claudia Marques
- Chris P Ponting
Wellcome (WT100981/z/13/z)
- Roderick N Carter
- Nicholas M Morton
Medical Research Council
- Wilfried Haerty
- Chris P Ponting
Diabetes UK
- Lisa C Heather
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2019, Sirey et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The long non-coding RNA Cerox1 is a post transcriptional regulator of mitochondrial complex I catalytic activity
eLife 8:e45051.
https://doi.org/10.7554/eLife.45051
Further reading
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- Biochemistry and Chemical Biology
- Structural Biology and Molecular Biophysics
Dynamic conformational and structural changes in proteins and protein complexes play a central and ubiquitous role in the regulation of protein function, yet it is very challenging to study these changes, especially for large protein complexes, under physiological conditions. Here, we introduce a novel isobaric crosslinker, Qlinker, for studying conformational and structural changes in proteins and protein complexes using quantitative crosslinking mass spectrometry. Qlinkers are small and simple, amine-reactive molecules with an optimal extended distance of ~10 Å, which use MS2 reporter ions for relative quantification of Qlinker-modified peptides derived from different samples. We synthesized the 2-plex Q2linker and showed that the Q2linker can provide quantitative crosslinking data that pinpoints key conformational and structural changes in biosensors, binary and ternary complexes composed of the general transcription factors TBP, TFIIA, and TFIIB, and RNA polymerase II complexes.
