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PreprintCited by 41RNA and protein synthesis mechanismsRNA modifications and cancerMitochondrial Function and Pathology

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Structural basis for human mitochondrial tRNA maturation

Open access
Meynier, Vincent, Hardwick, Steven W., Catala, Marjorie, Roske, Jonas, Oerum, Stephanie, Chirgadze, Dimitri Y., Barraud, Pierre, Yu, Wyatt, Luisi, Ben F., Tisné, Carine·2023·Nature Communications
DOI 10.1101/2023.12.19.572246PMC PMC11144196

Preprint — published as 10.1038/s41467-024-49132-0

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Abstract

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), 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 a tRNA methyltransferase complex in mt-RNase P cleavage activity is not fully understood. Moreover, the mechanisms of pre-tRNA 3’-cleavage and CCA addition have also yet to be uncovered. Here we report cryo-EM structures that visualise these events, revealing the molecular basis for the first steps of RNA-transcript processing in human mitochondria. Altogether, the structures 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 tRNA processing. The methyltransferase subcomplex recognises the pre-tRNA in a distinct mode that can support tRNA processing and 3’-CCA addition, likely resulting from an evolutionary adaptation of mitochondrial tRNA maturation complexes to the structurally-variable mitochondrial tRNAs. This subcomplex can also ensure a tRNA-folding quality-control checkpoint before the sequential docking of the maturation enzymes.

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Metadata

Authors
Meynier, V., Hardwick, S. W., Catala, M., Roske, J., Oerum, S., Chirgadze, D. Y., Barraud, P., Yu, W., Luisi, B. F., & Tisné, C.
Affiliations
  • Centre National de la Recherche Scientifique (FR)
  • University of Cambridge (GB)
Corresponding author
Tisné, Carine
ORCID
Venue
Nature Communications
Publisher
openRxiv
Published
2023-12-20
Volume
15
Issue
1
Pages
4683-4683
ISSN
2041-1723 (ISSN-L)
DOI
10.1101/2023.12.19.572246
PMC
PMC11144196
OpenAlex
W4399259643
Cited by
41
References
1
Citations by year
2026: 16 · 2025: 16 · 2024: 9
FWCI
5.58
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, cc-by)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Newcastle University ePrints (Newcastle Univesity) (cc-by)
Funders
  • Wellcome Trust (200873/Z/16/Z, 222451/Z/21/Z)
  • Agence Nationale de la Recherche (ANR‐19, ANR-19-CE07-0028, UMR8261, ANR-11-LABX-0011)
  • Centre National de la Recherche Scientifique (ANR-11-LABX-0011, UMR 8261)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
Keywords
mitochondrial genome, cryo-EM structure, RNA processing
MeSH terms
RNA, Mitochondrial, Humans, Methylation, Mitochondria, Models, Molecular, Nucleic Acid Conformation, RNA Precursors, RNA Processing, Post-Transcriptional, RNA, Transfer, tRNA Methyltransferases, Cryoelectron Microscopy, Ribonuclease P

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