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

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 posttranscriptionally 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.

lncRNA Spehd Regulates Hematopoietic Stem and Progenitor Cells and Is Required for Multilineage Differentiation

“…Even a slight defect in this pathway has the potential to be detrimental during a process in which cells exit a quiescent state and must undergo a rapid expansion, giving rise to a myriad of differentiated cell types. A recent report has identified the lncRNA here annotated as lnc6689 ( 2810468N07Rik ) also as being a regulator of oxidative phosphorylation in a microRNA-dependent manner (Sirey et al., 2018). Of course, the major questions that remain are a challenge in lncRNA biology more broadly—by what mechanism precisely does this non-coding RNA regulate the differentiation potential and the metabolic capacity of HSCs.…”

LncRNA Spehd regulates hematopoietic stem cells and progenitors and is required for multilineage differentiation

“…Even a slight defect in this pathway has the potential to be detrimental during a process where cells exit a quiescent state and have to undergo a rapid expansion, giving rise to a myriad of differentiated cell types. Intriguingly, a recent report has identified the lncRNA here annotated as lnc6689 (2810468N07Rik) also as a regulator of oxidative phosphorylation in a microRNA-dependent manner (Sirey et al, 2018). Of course, the major questions that remain are a challenge in lncRNA biology more broadly, namely by what mechanism precisely does this non-coding RNA regulate the differentiation potential and the metabolic capacity of HSCs.…”