The long non-coding RNA Cerox1 is a post transcriptional regulator of 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 rem...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2019-05-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/45051 |
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| author | Tamara M Sirey Kenny Roberts Wilfried Haerty Oscar Bedoya-Reina Sebastian Rogatti-Granados Jennifer Y Tan Nick Li Lisa C Heather Roderick N Carter Sarah Cooper Andrew J Finch Jimi Wills Nicholas M Morton Ana Claudia Marques Chris P Ponting |
| author_facet | Tamara M Sirey Kenny Roberts Wilfried Haerty Oscar Bedoya-Reina Sebastian Rogatti-Granados Jennifer Y Tan Nick Li Lisa C Heather Roderick N Carter Sarah Cooper Andrew J Finch Jimi Wills Nicholas M Morton Ana Claudia Marques Chris P Ponting |
| author_sort | Tamara M Sirey |
| collection | DOAJ |
| 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. |
| format | Article |
| id | doaj-art-7203b3e44ab34c76a17f006cfd21d380 |
| institution | Kabale University |
| issn | 2050-084X |
| language | English |
| publishDate | 2019-05-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj-art-7203b3e44ab34c76a17f006cfd21d3802025-02-03T14:55:25ZengeLife Sciences Publications LtdeLife2050-084X2019-05-01810.7554/eLife.45051The long non-coding RNA Cerox1 is a post transcriptional regulator of mitochondrial complex I catalytic activityTamara M Sirey0https://orcid.org/0000-0001-5606-2858Kenny Roberts1https://orcid.org/0000-0001-6155-0821Wilfried Haerty2https://orcid.org/0000-0003-0111-191XOscar Bedoya-Reina3Sebastian Rogatti-Granados4https://orcid.org/0000-0002-8438-7999Jennifer Y Tan5Nick Li6Lisa C Heather7https://orcid.org/0000-0002-7246-1338Roderick N Carter8Sarah Cooper9Andrew J Finch10https://orcid.org/0000-0002-8065-4623Jimi Wills11https://orcid.org/0000-0003-1669-007XNicholas M Morton12https://orcid.org/0000-0001-8218-8462Ana Claudia Marques13https://orcid.org/0000-0001-5174-8092Chris P Ponting14https://orcid.org/0000-0003-0202-7816MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom; MRC Functional Genomics Unit, University of Oxford, Oxford, United KingdomMRC Functional Genomics Unit, University of Oxford, Oxford, United KingdomMRC Functional Genomics Unit, University of Oxford, Oxford, United KingdomMRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom; MRC Functional Genomics Unit, University of Oxford, Oxford, United KingdomMRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom; MRC Functional Genomics Unit, University of Oxford, Oxford, United KingdomMRC Functional Genomics Unit, University of Oxford, Oxford, United KingdomMRC Functional Genomics Unit, University of Oxford, Oxford, United KingdomDepartment of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United KingdomUniversity/British Heart Foundation Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, United KingdomDepartment of Biochemistry, University of Oxford, Oxford, United KingdomMRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, United KingdomMRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, United KingdomUniversity/British Heart Foundation Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh, Edinburgh, United KingdomMRC Functional Genomics Unit, University of Oxford, Oxford, United KingdomMRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom; MRC Functional Genomics Unit, University of Oxford, Oxford, United KingdomTo 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.https://elifesciences.org/articles/45051mitochondriaenergy metabolismlong noncoding RNAmiRNApost-transcriptional regulation |
| spellingShingle | Tamara M Sirey Kenny Roberts Wilfried Haerty Oscar Bedoya-Reina Sebastian Rogatti-Granados Jennifer Y Tan Nick Li Lisa C Heather Roderick N Carter Sarah Cooper Andrew J Finch Jimi Wills Nicholas M Morton Ana Claudia Marques Chris P Ponting The long non-coding RNA Cerox1 is a post transcriptional regulator of mitochondrial complex I catalytic activity eLife mitochondria energy metabolism long noncoding RNA miRNA post-transcriptional regulation |
| title | The long non-coding RNA Cerox1 is a post transcriptional regulator of mitochondrial complex I catalytic activity |
| title_full | The long non-coding RNA Cerox1 is a post transcriptional regulator of mitochondrial complex I catalytic activity |
| title_fullStr | The long non-coding RNA Cerox1 is a post transcriptional regulator of mitochondrial complex I catalytic activity |
| title_full_unstemmed | The long non-coding RNA Cerox1 is a post transcriptional regulator of mitochondrial complex I catalytic activity |
| title_short | The long non-coding RNA Cerox1 is a post transcriptional regulator of mitochondrial complex I catalytic activity |
| title_sort | long non coding rna cerox1 is a post transcriptional regulator of mitochondrial complex i catalytic activity |
| topic | mitochondria energy metabolism long noncoding RNA miRNA post-transcriptional regulation |
| url | https://elifesciences.org/articles/45051 |
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