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Lookup NU author(s): Steven Hardwick, Professor Wyatt YueORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© The Author(s) 2024. The human mitochondrial genome is transcribed into two RNAs, containing mRNAs, rRNAs and tRNAs, all dedicated to produce essential proteins of the respiratory chain. The precise excision of tRNAs by the mitochondrial endoribonucleases (mt-RNase), P and Z, releases all RNA species from the two RNA transcripts. The tRNAs then undergo 3′-CCA addition. In metazoan mitochondria, RNase P is a multi-enzyme assembly that comprises the endoribonuclease PRORP and a tRNA methyltransferase subcomplex. The requirement for this tRNA methyltransferase subcomplex for mt-RNase P cleavage activity, as well as the mechanisms of pre-tRNA 3′-cleavage and 3′-CCA addition, are still poorly understood. Here, we report cryo-EM structures that visualise four steps of mitochondrial tRNA maturation: 5′ and 3′ tRNA-end processing, methylation and 3′-CCA addition, and explain the defined sequential order of the tRNA processing steps. The methyltransferase subcomplex recognises the pre-tRNA in a distinct mode that can support tRNA-end processing and 3′-CCA addition, likely resulting from an evolutionary adaptation of mitochondrial tRNA maturation complexes to the structurally-fragile mitochondrial tRNAs. This subcomplex can also ensure a tRNA-folding quality-control checkpoint before the sequential docking of the maturation enzymes. Altogether, our study provides detailed molecular insight into RNA-transcript processing and tRNA maturation in human mitochondria.© The Author(s) 2024.Mitochondrial tRNAs are less structurally stable than nuclear tRNAs, and their maturation pathway is unique. Here, the authors reveal how human mitochondrial precursor tRNAs are recognised, processed, methylated and prepared for full functionality in mitochondrial translation.
Author(s): Meynier V, Hardwick SW, Catala M, Roske JJ, Oerum S, Chirgadze DY, Barraud P, Yue WW, Luisi BF, Tisne C
Publication type: Article
Publication status: Published
Journal: Nature Communications
Year: 2024
Volume: 15
Online publication date: 01/06/2024
Acceptance date: 21/05/2024
Date deposited: 12/09/2024
ISSN (electronic): 2041-1723
Publisher: Springer Nature
URL: https://doi.org/10.1038/s41467-024-49132-0
DOI: 10.1038/s41467-024-49132-0
Data Access Statement: The data supporting the findings of this study are available from the corresponding authors upon request. The atomic coordinates and the cryo-EM maps have been deposited in the Protein data Bank (PDB) and in the Electron Microscopy Data Bank (EMDB), respectively, under the following accession codes: PDB 8CBO and EMD-16547 for Complex 1, PDB 8CBK and EMD-16544 for Complex 2, PDB ID 8CBL and EMD-16543 for Complex 3, PDB 8CBM and EMD-16545 for Complex 4. Source data are provided with this paper.
PubMed id: 38824131
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