Movie
Controller
Structure viewers
About Yorodumi Papers
+Search query
-Structure paper
| Title | Structural basis of substrate recognition by human tRNA splicing endonuclease TSEN. |
|---|---|
| Journal, issue, pages | Nat Struct Mol Biol, Vol. 30, Issue 6, Page 834-840, Year 2023 |
| Publish date | May 25, 2023 |
 Authors | Samoil Sekulovski / Lukas Sušac / Lukas S Stelzl / Robert Tampé / Simon Trowitzsch /  |
| PubMed Abstract | Heterotetrameric human transfer RNA (tRNA) splicing endonuclease TSEN catalyzes intron excision from precursor tRNAs (pre-tRNAs), utilizing two composite active sites. Mutations in TSEN and its ...Heterotetrameric human transfer RNA (tRNA) splicing endonuclease TSEN catalyzes intron excision from precursor tRNAs (pre-tRNAs), utilizing two composite active sites. Mutations in TSEN and its associated RNA kinase CLP1 are linked to the neurodegenerative disease pontocerebellar hypoplasia (PCH). Despite the essential function of TSEN, the three-dimensional assembly of TSEN-CLP1, the mechanism of substrate recognition, and the structural consequences of disease mutations are not understood in molecular detail. Here, we present single-particle cryogenic electron microscopy reconstructions of human TSEN with intron-containing pre-tRNAs. TSEN recognizes the body of pre-tRNAs and pre-positions the 3' splice site for cleavage by an intricate protein-RNA interaction network. TSEN subunits exhibit large unstructured regions flexibly tethering CLP1. Disease mutations localize far from the substrate-binding interface and destabilize TSEN. Our work delineates molecular principles of pre-tRNA recognition and cleavage by human TSEN and rationalizes mutations associated with PCH. |
 External links | Nat Struct Mol Biol / PubMed:37231152 |
| Methods | EM (single particle) |
| Resolution | 3.09 - 3.8 Å |
| Structure data | EMDB-14923, PDB-7zrz:  EMDB-14925: Human TSEN with pre-tRNA-Tyr-GTA |
| Source |
|
 Keywords |  RNA BINDING PROTEIN / RNP / endonuclease / tRNA / splicing |
