ジャーナル: Nat Struct Mol Biol / 年: 2025 タイトル: Molecular basis of human nuclear and mitochondrial tRNA 3' processing. 著者: Arjun Bhatta / Bernhard Kuhle / Ryan D Yu / Lucas Spanaus / Katja Ditter / Katherine E Bohnsack / Hauke S Hillen / 要旨: 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 ...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.