Abstract
Maturation of human mitochondrial tRNA is essential for cellular energy production, yet the underlying mechanisms remain only partially understood. Here, we present several cryo-EM structures of the mitochondrial RNase Z complex (ELAC2/SDR5C1/TRMT10C) bound to different maturation states of mitochondrial tRNAHis, showing the molecular basis for tRNA-substrate selection and catalysis. Our structural insights provide a molecular rationale for the 5'-to-3' tRNA processing order in mitochondria, the 3'-CCA antideterminant effect, and the basis for sequence-independent recognition of mitochondrial tRNA substrates. Furthermore, our study links mutations in ELAC2 to clinically relevant mitochondrial diseases, offering a deeper understanding of the molecular defects contributing to these conditions.
Keywords:
Cryo-EM; ELAC2; Mitochondria; RNA Processing; RNase Z.
© 2024. The Author(s).
MeSH terms
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Cryoelectron Microscopy
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Endoribonucleases* / chemistry
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Endoribonucleases* / genetics
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Endoribonucleases* / metabolism
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Humans
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Methyltransferases
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Mitochondria* / metabolism
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Mitochondrial Diseases / genetics
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Mitochondrial Diseases / metabolism
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Mitochondrial Proteins / chemistry
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Mitochondrial Proteins / genetics
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Mitochondrial Proteins / metabolism
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Models, Molecular
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Mutation
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Neoplasm Proteins
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RNA Processing, Post-Transcriptional
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RNA, Mitochondrial / chemistry
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RNA, Mitochondrial / genetics
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RNA, Mitochondrial / metabolism
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RNA, Transfer / chemistry
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RNA, Transfer / genetics
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RNA, Transfer / metabolism
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RNA, Transfer, His / chemistry
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RNA, Transfer, His / genetics
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RNA, Transfer, His / metabolism
Substances
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Endoribonucleases
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ELAC2 protein, human
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Mitochondrial Proteins
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TRMT10c protein, human
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RNA, Transfer, His
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RNase Z
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RNA, Transfer
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RNA, Mitochondrial
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Methyltransferases
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Neoplasm Proteins