Mitochondrial study offers new insights into how our cells process RNA for energy production

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Researchers at the Department of Cell and Molecular Biology, Karolinska Institutet have made a major discovery in how human cells produce energy. Their study, published in The EMBO Journal, reveals the detailed mechanisms of how mitochondria process transfer RNA (tRNA) molecules, which are essential for energy production.

Mitochondria need properly processed tRNAs to make proteins for energy. Problems in tRNA processing can lead to serious mitochondrial diseases. Until now, the exact process of tRNA maturation in mitochondria was not well understood.

"Our study reveals, at a molecular level, how the mitochondrial RNase Z complex recognizes and processes tRNA molecules," said Genís Valentín Gesé, the first author of the study. "By using advanced cryo-electron microscopy, we've been able to visualize the complex in action, capturing snapshots of tRNA at different stages of maturation. This is a significant step forward in understanding how our cells produce energy and maintain healthy function."

Using advanced cryo-electron microscopy, the researchers visualized the mitochondrial RNase Z complex, which is crucial for tRNA maturation. They captured high-resolution images showing how this complex processes tRNA molecules step-by-step.

"Seeing the RNase Z complex in such detail is like watching the gears of a finely tuned engine," explained Valentín Gesé. "We can observe how each component interacts with the tRNA, providing us with invaluable insights into the precise mechanisms of tRNA maturation."

Unveiling the sequential processing mechanism

One key finding is the discovery of the 5′-to-3′ processing order of tRNAs, which ensures they are correctly prepared for protein synthesis. The study also explains how the RNase Z complex avoids cutting tRNAs that already have their essential 3′-CCA tail, preventing errors in tRNA processing.

"Understanding the directionality of tRNA processing is crucial," said Martin Hällberg, senior author of the study. "It ensures that the tRNA molecules are properly matured and functional, which is essential for the mitochondria to produce energy efficiently."

Importantly, the research links specific mutations in the ELAC2 gene to mitochondrial diseases. Understanding these mutations helps in developing targeted therapies for conditions like cardiomyopathy and intellectual disabilities.

"By visualizing where these mutations occur and how they affect the structure and function of the RNase Z complex, we can understand the molecular basis of certain mitochondrial diseases," explains Hällberg. "This knowledge is crucial for developing targeted therapies to correct or compensate for these defects."

This breakthrough offers new pathways for diagnosing and treating mitochondrial diseases and enhances our overall understanding of mitochondrial biology.

More information: Genís Valentín Gesé et al, Structural basis of 3′-tRNA maturation by the human mitochondrial RNase Z complex, The EMBO Journal (2024). DOI: 10.1038/s44318-024-00297-w

Journal information: EMBO Journal

Provided by Karolinska Institutet