A new regulatory molecule in mitochondria opens a new research field
Scientists at the University of Gothenburg and Karolinska Institute have identified a particular molecule that regulates the expression of mitochondrial genes in human cells. Their study is published in the journal Cell. In the long term, the discovery may enable new therapies for several severe diseases.
Mitochondria are found in almost all the body’s cells, and their key function is to convert energy from our food into the form of energy that the cells can use. Therefore, the term “mitochondrion” (singular) is frequently used to refer to the cells’ power station, but it also plays a crucial part in cell growth and controlled cell death.
Unlike other parts of the cell, the mitochondrion has its own DNA. Damage to mitochondrial DNA can cause severe diseases that affect the brain, heart, and other tissues that require abundant energy. This study shows that 7S RNA, a non-coding RNA molecule*, regulates mitochondrial gene expression.
Opens new field
The study was headed by Professor Maria Falkenberg of Sahlgrenska Academy, University of Gothenburg, jointly with Martin Hällberg, senior researcher at Karolinska Institute.
“This is a new principle for regulating mitochondrial activity. The discovery makes it possible to develop therapies that can control 7S RNA production, which may be valuable in treating diseases involving disrupted mitochondrial function,” says Maria Falkenberg.
“The finding creates a whole new field in mitochondrial research. We’re just embarking on the work, and it’s going to take several years to explore the practical implications of our new finding,” Hällberg says.
New mechanism
Numerous non-coding RNA molecules are necessary for proper development in mammals. Still, non-coding RNAs were not formerly thought to play any part in regulating gene activity inside the mitochondrion. Levels of mitochondrial 7S RNA were known to vary depending on the cell’s metabolism. This study shows how the change affects mitochondria and gives us a detailed molecular understanding of how this takes place. The researchers involved have jointly developed methods of studying the effects of 7S RNA, both on purified proteins and mitochondrial gene activity in cells. The study reveals a probable mechanism for how 7S RNA regulates gene expression in human mitochondria.
Physiological enigma
Three researchers share the first authorship of the study in the journal Cell: Xuefeng Zhu (University of Gothenburg), Xie Xie (University of Gothenburg), and Hrishikesh Das (Karolinska Institute).
“The most exciting thing about this study is that we’ve identified an entirely new mechanism for regulating mitochondrial activity. Our findings reveal that 7S RNA, a molecule identified 40 years ago, has this function. Although 7S RNA is found in large quantities and often measured in studies of mitochondrial function, its physiological role has remained an enigma,” says Xuefeng Zhu, one of the University of Gothenburg researchers.
Non-coding RNA molecules play a key role in regulating various processes inside the nucleus. Still, the fact that this type of molecule can also control processes in the mitochondrion was not previously known.
“Our finding reveals a new and physiologically relevant level of regulation in human mitochondria. Now, the challenge is to understand how 7S RNA levels are fine-tuned in response to the metabolic requirements of the human cell. We have ideas, and we’re going to try and explore them over the next few years,” says Xie Xie. Having carried out the work as a postdoctoral fellow in the group at the University of Gothenburg, she now works as a researcher at Pretzel Therapeutics. This start-up develops new ways of managing mitochondrial dysfunction.
The research was funded by the Swedish Research Council, the Swedish Cancer Society, ALF Västra Götaland, the European Research Council, and the Knut and Alice Wallenberg Foundation. Access to microscopy at the Centre for Cellular Imaging have had great importance for the implementation of the study.
Title: Non-coding 7S RNA inhibits transcription via mitochondrial RNA polymerase dimerization
The genetic information in our cells is transferred to proteins from DNA by means of RNA (ribonucleic acid). However, the protein-coding makes up only 1.5 percent of the whole human genome and, moreover, other, noncoding parts of our genome are also used as templates for RNA formation. In recent years, scientists have realized that although these noncoding RNA molecules do not result in protein production, they perform other extremely important biological functions.
