Non-Coding 7S RNA Found to Regulate Mitochondrial Gene Expression

Researchers in Sweden and Germany have discovered that a non-coding RNA molecule frequently measured but with unknown physiological role actually regulates mitochondrial gene expression in human cells.

The findings are significant because altered mitochondrial transcription drives a number of human pathologies. A peculiar aspect of mitochondria is the existence of a separate mitochondrial genome, which, when damaged, can cause serious diseases, affecting high-energy tissues like the brain and heart. Hence, it is crucial to study how mitochondrial gene expression is regulated and to find ways to control this process with therapies.

Human mitochondrial 7S RNA belongs to a large family of non-coding RNA molecules essential for proper development in mammals. It was previously known that levels of mitochondrial 7S RNA vary depending on the metabolic needs of the eukaryotic cell, but the molecular basis and functional implications for these changes were unknown.

To better understand this process, researchers from the University of Gothenburg and Karolinska Institutet, both in Sweden, and the University of Cologne in Germany, jointly developed methods to study the effects of 7S RNA both on purified proteins and mitochondrial gene activity in cells. Using Cryo-EM, they were able to show the probable mechanism for how 7S RNA inhibits mitochondrial gene activity.

“The most exciting thing about the study is that we identify a completely new mechanism for regulation of mitochondrial activity,” says Xuefeng Zhu. Xuefeng, and Xie Xie, both at University of Gothenburg. “Our findings reveal the function of 7S RNA, a molecule identified already 40 years ago. Despite 7S RNA being abundant and frequently measured in studies of mitochondrial function, its physiological role has remained an enigma until now.”

The challenge now is to understand how 7S RNA levels are fine-tuned in response to the metabolic needs of the human cell. We have ideas and will try to explore them in the years to come,” says Xie Xie, who performed the work as a postdoctoral student at University of Gothenburg.

Although the practical implications of the findings will take years to explore, future therapies targeting 7S RNA production, can be valuable, according to Martin Hällberg at Karolinska Insititutet. “These are early days, but this will open a new field in mitochondrial research.”

The findings were published recently in Cell.