8HMY

Cryo-EM structure of the human pre-catalytic TSEN/pre-tRNA complex

Summary for 8HMY

• Entry DOI: 10.2210/pdb8hmy/pdb
• EMDB information: 34904
• Descriptor: tRNA-splicing endonuclease subunit Sen2, tRNA-splicing endonuclease subunit Sen34, Pre-tRNA, ... (7 entities in total)
• Functional Keywords: pre-trna splicing, tsen, pre-trna, rna binding protein/rna, rna binding protein-rna complex
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 261762.94

Authors

Zhang, X.,Yang, F.,Zhan, X.,Shi, Y. (deposition date: 2022-12-06, release date: 2023-04-19, Last modification date: 2024-05-29)

Primary citation

Zhang, X.,Yang, F.,Zhan, X.,Bian, T.,Xing, Z.,Lu, Y.,Shi, Y.
Structural basis of pre-tRNA intron removal by human tRNA splicing endonuclease.
Mol.Cell, 83:1328-1339.e4, 2023

PubMed Abstract: 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.

PubMed: 37028420
DOI: 10.1016/j.molcel.2023.03.015

Experimental method

ELECTRON MICROSCOPY (2.94 Å)