Study identifies the regulatory function of non-coding 7S RNA

In human cells, a non-coding RNA molecule controls mitochondrial gene expression, according to new research published in the journal Cell. The research is the result of a collaboration between Sweden’s University of Gothenburg and Karolinska Institutet, as well as Germany’s University of Cologne.

Study identifies the regulatory function of non-coding 7S RNA
Maria Falkenberg, Sahlgrenska Academy at the University of Gothenburg. Image Credit: Johan Wingborg.

Mitochondria are the cells’ powerhouses, transforming energy from the food into the form of energy needed for different cellular functions. The existence of a distinct mitochondrial genome, which when damaged, can cause severe diseases affecting high-energy tissues such as the brain and heart, is a unique feature of mitochondria.

As a result, it is critical to investigate how mitochondrial gene expression is controlled in search of ways to regulate this process with therapies in the long run.

Human mitochondrial 7S RNA is part of a huge family of non-coding RNA molecules that are required for proper mammalian development. Although it was earlier known that mitochondrial 7S RNA levels fluctuate depending on the metabolic requirements of the eukaryotic cell, the molecular basis and functional implications of these changes were uncertain.

The researchers devised methods to investigate the effects of 7S RNA on purified proteins as well as mitochondrial gene activity in cells.

The most exciting thing about the study is that we identify a completely new mechanism for regulation of mitochondrial activity. 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.

Xuefeng Zhu, University of Gothenburg

Xuefeng Zhu adds, “We are thrilled that we, in collaboration, could determine a cryo-EM structure that shows the probable mechanism for how 7S RNA inhibits mitochondrial gene activity.”

Xuefeng Zhu and Xie Xie, both from the University of Gothenburg, are co-first authors on the paper with Karolinska Institutet’s Hrishikesh Das.

Although non-coding RNA molecules perform a vital role in the regulation of different processes in the nucleus, no specific role in mitochondrial function regulation has been identified.

Our finding reveals a new and physiologically relevant level of regulation in human mitochondria. 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.”

Xie Xie, University of Gothenburg

Xie Xie, who did the research as a postdoctoral student at the University of Gothenburg, is now a scientist at Pretzel Therapeutics, a start-up focused on finding new ways to treat mitochondrial dysfunction.

This is a new principle for regulating mitochondrial activity and future therapies targeting 7S RNA production, can be valuable.”

Maria Falkenberg, Professor, University of Gothenburg

Maria Falkenberg headed the research along with Martin Hällberg at Karolinska Insititutet.

However, it will take years to investigate the work’s practical implications. “These are early days, but this will open a new field in mitochondrial research,” remarks Martin Hällberg.

Source:
Journal reference:

Zhu, X., et al. (2022) Non-coding 7S RNA inhibits transcription via mitochondrial RNA polymerase dimerization. Cell. doi.org/10.1016/j.cell.2022.05.006.

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