Institute of Genetics and Cancer

Fine tuning energy production

Cerox1 long non-coding RNA regulates mitochondrial activity


Every cell in the body needs energy to perform its daily tasks.  More than 90% of this energy is generated by tiny power stations inside each cell called mitochondria.  Thousands of proteins are needed to make each functional mitochondrion and their amounts must be tightly regulated. This regulation can occur by altering the levels of messenger RNA (mRNA) that contain instructions for making these proteins.  Short pieces of RNA can help control the amount of mRNA in cells. MicroRNAs (miRNA) can reduce the amount and other RNAs, such as long noncoding RNAs (lncRNAs) can prevent this by acting as a decoy  for these miRNAs.

Chris Ponting, Tamara Sirey and colleagues investigated whether a lncRNA called Cerox1 could be regulating the amount of mRNA available for making mitochondrial proteins by acting as a decoy for a miRNA. Scientists know little about how mRNAs encoding mitochondrial proteins are regulated in a concerted manner.  The researchers hoped to shed light upon how a choreography of RNA interactions maintains the fundamental biological process of energy equilibrium.

The researchers found that mouse Cerox1 controls the mRNA abundance of at least 12 proteins involved in mitochondrial energy production. This happens through binding to the miRNA miR-488-3p.  By changing the amount of Cerox1 they found that when its levels are high then energy production increases and cellular stress decreases, and when its levels are low there are opposite effects.  The study then found that the human version of the lncRNA, CEROX1, also regulates mitochondrial energy production in human cells suggesting that this is a mechanism that is conser

ved across placental mammalian evolution.

Altered mitochondrial energy production is observed in healthy aging and in many disparate diseases such as Parkinson’s disease, type II diabetes and cardiovascular disease.  Whilst mitochondrial dysfunction is not necessarily causative of these diseases, poor energy production places a large, additional stress upon an affected cell.  Understanding how a novel lncRNA molecule modulates this fundamental biological process could open up new areas of therapy to help alleviate dysfunctional energy production in disease.