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Structure paper

TitleMolecular basis of human nuclear and mitochondrial tRNA 3' processing.
Journal, issue, pagesNat Struct Mol Biol, Vol. 32, Issue 4, Page 613-624, Year 2025
Publish dateJan 2, 2025
AuthorsArjun Bhatta / Bernhard Kuhle / Ryan D Yu / Lucas Spanaus / Katja Ditter / Katherine E Bohnsack / Hauke S Hillen /
PubMed AbstractEukaryotic 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 ...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.
External linksNat Struct Mol Biol / PubMed:39747487 / PubMed Central
MethodsEM (single particle)
Resolution2.93 - 4.0 Å
Structure data

EMDB-19453, PDB-8rr1:
Human mitochondrial RNase Z complex with ELAC2-D550N catalytic mutant and tRNA-Tyr precursor (Composite model)
Method: EM (single particle) / Resolution: 2.93 Å

EMDB-19454: Consensus map of human mitochondrial RNase Z complex with ELAC2-D550N mutant and tRNA-Gln precursor
Method: EM (single particle) / Resolution: 3.0 Å

EMDB-19455, PDB-8rr3:
Human mitochondrial RNase Z complex with ELAC2-D550N catalytic mutant and tRNA-Gln precursor (Composite model)
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-19456: Consensus refinement map of human mitochondrial RNase Z complex with tRNA-Gln precursor
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-19457, PDB-8rr4:
Human mitochondrial RNase Z complex with ELAC2-D550N catalytic mutant with ordered flexible arm and tRNA-Tyr precursor - (Composite model)
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-19458: Consensus map of human mitochondrial RNase Z complex with tRNA-Tyr precursor (Class with ordered ELAC2 flexible arm)
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-19469: Human mitochondrial RNase Z complex with tRNA-Tyr precursor - Focused map around ELAC2
Method: EM (single particle) / Resolution: 3.22 Å

EMDB-19470: Human mitochondrial RNase Z complex with tRNA-Gln precursor - Focused map around ELAC2
Method: EM (single particle) / Resolution: 4.0 Å

EMDB-19471: Human mitochondrial RNase Z complex with tRNA-Tyr precursor and ordered ELAC2 flexible arm - ELAC2 focused map
Method: EM (single particle) / Resolution: 3.6 Å

Chemicals

ChemComp-ZN:
Unknown entry

ChemComp-SAH:
S-ADENOSYL-L-HOMOCYSTEINE

Source
  • homo sapiens (human)
KeywordsRNA BINDING PROTEIN / tRNA processing / RNase Z / endonuclease / mitochondrial

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