Structural basis for human mitochondrial tRNA maturation.
Humans
RNA, Transfer
/ metabolism
Mitochondria
/ metabolism
Ribonuclease P
/ metabolism
tRNA Methyltransferases
/ metabolism
RNA Processing, Post-Transcriptional
Cryoelectron Microscopy
RNA, Mitochondrial
/ metabolism
Methylation
Nucleic Acid Conformation
Models, Molecular
RNA Precursors
/ metabolism
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
01 Jun 2024
01 Jun 2024
Historique:
received:
01
12
2023
accepted:
21
05
2024
medline:
2
6
2024
pubmed:
2
6
2024
entrez:
1
6
2024
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 38824131
doi: 10.1038/s41467-024-49132-0
pii: 10.1038/s41467-024-49132-0
doi:
Substances chimiques
RNA, Transfer
9014-25-9
Ribonuclease P
EC 3.1.26.5
tRNA Methyltransferases
EC 2.1.1.-
RNA, Mitochondrial
0
PRORP protein, human
EC 3.1.26.5
RNA Precursors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4683Informations de copyright
© 2024. The Author(s).
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