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Mitochondrial tRNA biogenesis, modifications and disease relevance
Wen-Yu Zhu1, Ilias Skeparnias2, Athanasios-Nasir Shaukat2
1School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
Nature Reviews. Molecular Cell Biology
|July 24, 2026
Summary
Mitochondrial transfer RNAs (mt-tRNAs) have evolved unique structures and modifications for cellular function. This review explores their biogenesis, coevolution with cellular machinery, and roles in disease.
Area of Science:
- Mitochondrial biology
- Molecular genetics
- Evolutionary biology
Background:
- Mitochondrial transfer RNAs (mt-tRNAs) are crucial for protein synthesis within mitochondria.
- Their structure and function have undergone significant degeneration and adaptation during evolution.
- Post-transcriptional modifications are essential for maintaining mt-tRNA function.
Purpose of the Study:
- To review the biogenesis, maturation, and modifications of mt-tRNAs.
- To examine the coevolution of mt-tRNAs with mitochondrial aminoacyl-tRNA synthetases and mitoribosomes.
- To discuss the role of mt-tRNAs in pathologies and potential therapeutic strategies.
Main Methods:
- Literature review of recent advancements in mt-tRNA research.
- Analysis of evolutionary adaptations in mt-tRNA structure and associated proteomes.
- Synthesis of information on post-transcriptional modifications and their impact on function.
Main Results:
- mt-tRNAs are excised from polycistronic transcripts and mature via specific enzymes.
- Mitochondrial protein synthesis machinery has coevolved to recognize degenerated mt-tRNAs.
- Post-transcriptional modifications stabilize mt-tRNA structure, aid decoding, and link metabolism to translation.
Conclusions:
- Understanding mt-tRNA biogenesis and function is key to addressing mitochondrial diseases.
- Therapeutic strategies can be developed by targeting mt-tRNA processing and modification pathways.
- Restoring mitochondrial translation coherence is a critical goal for treating mt-tRNA-associated pathologies.
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