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

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

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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.

Original languageEnglish
Article numbere45051
JournaleLife
Volume8
DOIs
Publication statusPublished - 30 May 2019

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