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TitleStructural basis for pre-tRNA recognition and processing by the human tRNA splicing endonuclease complex.
Journal, issue, pagesNat Struct Mol Biol, Vol. 30, Issue 6, Page 824-833, Year 2023
Publish dateMay 25, 2023
AuthorsCassandra K Hayne / Kevin John U Butay / Zachary D Stewart / Juno M Krahn / Lalith Perera / Jason G Williams / Robert M Petrovitch / Leesa J Deterding / A Gregory Matera / Mario J Borgnia / Robin E Stanley /
PubMed AbstractThroughout bacteria, archaea and eukarya, certain tRNA transcripts contain introns. Pre-tRNAs with introns require splicing to form the mature anticodon stem loop. In eukaryotes, tRNA splicing is ...Throughout bacteria, archaea and eukarya, certain tRNA transcripts contain introns. Pre-tRNAs with introns require splicing to form the mature anticodon stem loop. In eukaryotes, tRNA splicing is initiated by the heterotetrameric tRNA splicing endonuclease (TSEN) complex. All TSEN subunits are essential, and mutations within the complex are associated with a family of neurodevelopmental disorders known as pontocerebellar hypoplasia (PCH). Here, we report cryo-electron microscopy structures of the human TSEN-pre-tRNA complex. These structures reveal the overall architecture of the complex and the extensive tRNA binding interfaces. The structures share homology with archaeal TSENs but contain additional features important for pre-tRNA recognition. The TSEN54 subunit functions as a pivotal scaffold for the pre-tRNA and the two endonuclease subunits. Finally, the TSEN structures enable visualization of the molecular environments of PCH-causing missense mutations, providing insight into the mechanism of pre-tRNA splicing and PCH.
External linksNat Struct Mol Biol / PubMed:37231153 / PubMed Central
MethodsEM (single particle)
Resolution3.28 - 3.93 Å
Structure data

26856

7uxa

EMDB-26856, PDB-7uxa:
Human tRNA Splicing Endonuclease Complex bound to pre-tRNA-ARG
Method: EM (single particle) / Resolution: 3.28 Å

EMDB-28755: Human tRNA Splicing Endonuclease Complex bound to 2'F-tRNA-Arg
Method: EM (single particle) / Resolution: 3.93 Å

Chemicals

ChemComp-MG:
Unknown entry

Source
  • homo sapiens (human)
  • synthetic construct (others)
KeywordsSPLICING/RNA / splicing endonuclease / pre-tRNA / TSEN / EndA / SPLICING-RNA complex

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