7uxa
From Proteopedia
Human tRNA Splicing Endonuclease Complex bound to pre-tRNA-ARG
Structural highlights
DiseaseSEN34_HUMAN Pontocerebellar hypoplasia type 2. The disease is caused by variants affecting the gene represented in this entry. FunctionSEN34_HUMAN Constitutes one of the two catalytic subunit of the tRNA-splicing endonuclease complex, a complex responsible for identification and cleavage of the splice sites in pre-tRNA. It cleaves pre-tRNA at the 5'- and 3'-splice sites to release the intron. The products are an intron and two tRNA half-molecules bearing 2',3'-cyclic phosphate and 5'-OH termini. There are no conserved sequences at the splice sites, but the intron is invariably located at the same site in the gene, placing the splice sites an invariant distance from the constant structural features of the tRNA body. It probably carries the active site for 3'-splice site cleavage. The tRNA splicing endonuclease is also involved in mRNA processing via its association with pre-mRNA 3'-end processing factors, establishing a link between pre-tRNA splicing and pre-mRNA 3'-end formation, suggesting that the endonuclease subunits function in multiple RNA-processing events.[1] Publication Abstract from PubMedThroughout 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. Structural basis for pre-tRNA recognition and processing by the human tRNA splicing endonuclease complex.,Hayne CK, Butay KJU, Stewart ZD, Krahn JM, Perera L, Williams JG, Petrovitch RM, Deterding LJ, Matera AG, Borgnia MJ, Stanley RE Nat Struct Mol Biol. 2023 Jun;30(6):824-833. doi: 10.1038/s41594-023-00991-z. , Epub 2023 May 25. PMID:37231153[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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