Structural basis of 3'-tRNA maturation by the human mitochondrial RNase Z complex.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 8208664 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1460-2075 (Electronic) Linking ISSN: 02614189 NLM ISO Abbreviation: EMBO J Subsets: MEDLINE

Publication: 2024- : [London] : Nature Publishing Group
Original Publication: Eynsham, Oxford, England : Published for the European Molecular Biology Organization by IRL Press, [c1982-

Mitochondria*/metabolism ; Endoribonucleases*/metabolism ; Endoribonucleases*/chemistry ; Endoribonucleases*/genetics; Humans ; Cryoelectron Microscopy ; Mitochondrial Proteins/metabolism ; Mitochondrial Proteins/genetics ; Mitochondrial Proteins/chemistry ; RNA, Transfer, His/metabolism ; RNA, Transfer, His/chemistry ; RNA, Transfer, His/genetics ; Models, Molecular ; Mutation ; RNA, Transfer/metabolism ; RNA, Transfer/genetics ; RNA, Transfer/chemistry ; RNA Processing, Post-Transcriptional ; RNA, Mitochondrial/metabolism ; RNA, Mitochondrial/genetics ; RNA, Mitochondrial/chemistry ; Mitochondrial Diseases/metabolism ; Mitochondrial Diseases/genetics ; Methyltransferases ; Neoplasm Proteins

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 tRNA ^His , 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.
Competing Interests: Disclosure and competing interests statement. The authors declare no competing interests.
(© 2024. The Author(s).)

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2017.0080 Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation); 2018.0080 Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation); 2018-03808 Vetenskapsrådet (VR); 2022-02326 Vetenskapsrådet (VR)

Keywords: Cryo-EM; ELAC2; Mitochondria; RNA Processing; RNase Z

EC 3.1.- (Endoribonucleases)
0 (ELAC2 protein, human)
0 (Mitochondrial Proteins)
EC 2.1.1.- (TRMT10c protein, human)
0 (RNA, Transfer, His)
EC 3.1.- (RNase Z)
9014-25-9 (RNA, Transfer)
0 (RNA, Mitochondrial)
EC 2.1.1.- (Methyltransferases)
0 (Neoplasm Proteins)

Date Created: 20241108 Date Completed: 20241216 Latest Revision: 20250117

20250129

PMC11649783

10.1038/s44318-024-00297-w

39516281