Structural basis of pre-tRNA intron removal by human tRNA splicing endonuclease.

Xiaofeng Zhang, Fenghua Yang, Xiechao Zhan, Tong Bian, Zhihan Xing, Yichen Lu, Yigong Shi

Molecular cell 2023 Apr 20

filter terms:

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. Copyright © 2023 Elsevier Inc. All rights reserved.

Citation

Xiaofeng Zhang, Fenghua Yang, Xiechao Zhan, Tong Bian, Zhihan Xing, Yichen Lu, Yigong Shi. Structural basis of pre-tRNA intron removal by human tRNA splicing endonuclease. Molecular cell. 2023 Apr 20;83(8):1328-1339.e4