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TitleStructural basis of pre-tRNA intron removal by human tRNA splicing endonuclease.
Journal, issue, pagesMol Cell, Vol. 83, Issue 8, Page 1328-11339.e4, Year 2023
Publish dateApr 20, 2023
AuthorsXiaofeng Zhang / Fenghua Yang / Xiechao Zhan / Tong Bian / Zhihan Xing / Yichen Lu / Yigong Shi /
PubMed AbstractRemoval of the intron from precursor-tRNA (pre-tRNA) is essential in all three kingdoms of life. In humans, this process is mediated by the tRNA splicing endonuclease (TSEN) comprising four subunits: ...Removal of the intron from precursor-tRNA (pre-tRNA) is essential in all three kingdoms of life. In humans, this process is mediated by the tRNA splicing endonuclease (TSEN) comprising four subunits: TSEN2, TSEN15, TSEN34, and TSEN54. Here, we report the cryo-EM structures of human TSEN bound to full-length pre-tRNA in the pre-catalytic and post-catalytic states at average resolutions of 2.94 and 2.88 Å, respectively. Human TSEN features an extended surface groove that holds the L-shaped pre-tRNA. The mature domain of pre-tRNA is recognized by conserved structural elements of TSEN34, TSEN54, and TSEN2. Such recognition orients the anticodon stem of pre-tRNA and places the 3'-splice site and 5'-splice site into the catalytic centers of TSEN34 and TSEN2, respectively. The bulk of the intron sequences makes no direct interaction with TSEN, explaining why pre-tRNAs of varying introns can be accommodated and cleaved. Our structures reveal the molecular ruler mechanism of pre-tRNA cleavage by TSEN.
External linksMol Cell / PubMed:37028420
MethodsEM (single particle)
Resolution2.9 - 2.94 Å
Structure data

34904

8hmy

EMDB-34904, PDB-8hmy:
Cryo-EM structure of the human pre-catalytic TSEN/pre-tRNA complex
Method: EM (single particle) / Resolution: 2.94 Å

34905

8hmz

EMDB-34905, PDB-8hmz:
Cryo-EM structure of the human post-catalytic TSEN/pre-tRNA complex
Method: EM (single particle) / Resolution: 2.9 Å

Chemicals

ChemComp-MG:
Unknown entry

Source
  • homo sapiens (human)
KeywordsRNA BINDING PROTEIN/RNA / pre-tRNA splicing / TSEN / pre-tRNA / RNA BINDING PROTEIN-RNA complex

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