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Structure paper

TitleStructural basis for human mitochondrial tRNA maturation.
Journal, issue, pagesNat Commun, Vol. 15, Issue 1, Page 4683, Year 2024
Publish dateJun 1, 2024
AuthorsVincent Meynier / Steven W Hardwick / Marjorie Catala / Johann J Roske / Stephanie Oerum / Dimitri Y Chirgadze / Pierre Barraud / Wyatt W Yue / Ben F Luisi / Carine Tisné /
PubMed AbstractThe 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 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.
External linksNat Commun / PubMed:38824131 / PubMed Central
MethodsEM (single particle)
Resolution2.47 - 4.5 Å
Structure data

EMDB-16543, PDB-8cbk:
Structure of human mitochondrial RNase P in complex with mitochondrial pre-tRNA-His(5,Ser)
Method: EM (single particle) / Resolution: 2.76 Å

EMDB-16544, PDB-8cbl:
Structure of human mitochondrial RNase Z in complex with mitochondrial pre-tRNA-His(0,Ser)
Method: EM (single particle) / Resolution: 2.79 Å

EMDB-16545, PDB-8cbm:
Structure of human mitochondrial CCA-adding enzyme in complex with mitochondrial pre-tRNA-Ile
Method: EM (single particle) / Resolution: 3.14 Å

EMDB-16547, PDB-8cbo:
Structure of human mitochondrial MRPP1-MRPP2 in complex with mitochondrial pre-tRNA-Ile
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-16667: Consensus Refinement - Map 1
Method: EM (single particle) / Resolution: 2.76 Å

EMDB-16668: Local refinement - Map 2
Method: EM (single particle) / Resolution: 2.74 Å

EMDB-16669: Cryo-EM structure of human mitochondrial RNase P in complex with mitochondrial pre-tRNA-His(5,Ser)
Method: EM (single particle) / Resolution: 4.5 Å

EMDB-16673: Consensus Refinement - Map 1
Method: EM (single particle) / Resolution: 2.79 Å

EMDB-16674: Local refinement - Map 2 (mask 1)
Method: EM (single particle) / Resolution: 2.47 Å

EMDB-16675: Local refinement - map 3 (Mask 2)
Method: EM (single particle) / Resolution: 4.05 Å

EMDB-16690: Consensus Refinement - Map 1
Method: EM (single particle) / Resolution: 3.14 Å

EMDB-16691: Local refinement - Map 2 (Mask 1)
Method: EM (single particle) / Resolution: 4.5 Å

EMDB-16692: Global Refinement - Map 1
Method: EM (single particle) / Resolution: 3.0 Å

Chemicals

ChemComp-NAD:
NICOTINAMIDE-ADENINE-DINUCLEOTIDE / NAD*YM / Nicotinamide adenine dinucleotide

ChemComp-ZN:
Unknown entry

ChemComp-SAH:
S-ADENOSYL-L-HOMOCYSTEINE / S-Adenosyl-L-homocysteine

ChemComp-MG:
Unknown entry

ChemComp-HOH:
WATER / Water

ChemComp-CDP:
CYTIDINE-5'-DIPHOSPHATE / Cytidine diphosphate

Source
  • homo sapiens (human)
KeywordsRNA BINDING PROTEIN / RNA maturation / RNA modification / mitochondrial tRNA / RNA methyltransferase / MRPP1 / MRPP2 / MRPP3 / m6A / RNA binding / RNA recognition

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