8RR4

Human mitochondrial RNase Z complex with ELAC2-D550N catalytic mutant with ordered flexible arm and tRNA-Tyr precursor - (Composite model)

Summary for 8RR4

• Entry DOI: 10.2210/pdb8rr4/pdb
• EMDB information: 19457
• Descriptor: 3-hydroxyacyl-CoA dehydrogenase type-2, Zinc phosphodiesterase ELAC protein 2, tRNA methyltransferase 10 homolog C, ... (6 entities in total)
• Functional Keywords: trna processing, rnase z, endonuclease, mitochondrial, rna binding protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 7
• Total formula weight: 263660.93

Authors

Bhatta, A.,Yu, R.D.,Kuhle, B.,Hillen, H.S. (deposition date: 2024-01-22, release date: 2025-01-08, Last modification date: 2025-04-23)

Primary citation

Bhatta, A.,Kuhle, B.,Yu, R.D.,Spanaus, L.,Ditter, K.,Bohnsack, K.E.,Hillen, H.S.
Molecular basis of human nuclear and mitochondrial tRNA 3' processing.
Nat.Struct.Mol.Biol., 32:613-624, 2025

PubMed Abstract: Eukaryotic transfer RNA (tRNA) precursors undergo sequential processing steps to become mature tRNAs. In humans, ELAC2 carries out 3' end processing of both nucleus-encoded (nu-tRNAs) and mitochondria-encoded (mt-tRNAs) tRNAs. ELAC2 is self-sufficient for processing of nu-tRNAs but requires TRMT10C and SDR5C1 to process most mt-tRNAs. Here we show that TRMT10C and SDR5C1 specifically facilitate processing of structurally degenerate mt-tRNAs lacking the canonical elbow. Structures of ELAC2 in complex with TRMT10C, SDR5C1 and two divergent mt-tRNA substrates reveal two distinct mechanisms of pre-tRNA recognition. While canonical nu-tRNAs and mt-tRNAs are recognized by direct ELAC2-RNA interactions, processing of noncanonical mt-tRNAs depends on protein-protein interactions between ELAC2 and TRMT10C. These results provide the molecular basis for tRNA 3' processing in both the nucleus and the mitochondria and explain the organelle-specific requirement for additional factors. Moreover, they suggest that TRMT10C-SDR5C1 evolved as a mitochondrial tRNA maturation platform to compensate for the structural erosion of mt-tRNAs in bilaterian animals.

PubMed: 39747487
DOI: 10.1038/s41594-024-01445-w

Experimental method

ELECTRON MICROSCOPY (3.2 Å)