7EVO

The cryo-EM structure of the human 17S U2 snRNP

7EVO の概要

• エントリーDOI: 10.2210/pdb7evo/pdb
• EMDBエントリー: 31334
• 分子名称: U2 snRNA, Splicing factor 3A subunit 3, HIV Tat-specific factor 1, ... (23 entities in total)
• 機能のキーワード: u2 snrnp, prp5, sf3b1, splicing
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 21
• 化学式量合計: 1061814.84

構造登録者

Zhang, X.,Zhan, X.,Shi, Y. (登録日: 2021-05-21, 公開日: 2022-08-03, 最終更新日: 2024-05-22)

主引用文献

Zhang, X.,Zhan, X.,Bian, T.,Yang, F.,Li, P.,Lu, Y.,Xing, Z.,Fan, R.,Zhang, Q.C.,Shi, Y.
Structural insights into branch site proofreading by human spliceosome.
Nat.Struct.Mol.Biol., 2024

PubMed Abstract: Selection of the pre-mRNA branch site (BS) by the U2 small nuclear ribonucleoprotein (snRNP) is crucial to prespliceosome (A complex) assembly. The RNA helicase PRP5 proofreads BS selection but the underlying mechanism remains unclear. Here we report the atomic structures of two sequential complexes leading to prespliceosome assembly: human 17S U2 snRNP and a cross-exon pre-A complex. PRP5 is anchored on 17S U2 snRNP mainly through occupation of the RNA path of SF3B1 by an acidic loop of PRP5; the helicase domain of PRP5 associates with U2 snRNA; the BS-interacting stem-loop (BSL) of U2 snRNA is shielded by TAT-SF1, unable to engage the BS. In the pre-A complex, an initial U2-BS duplex is formed; the translocated helicase domain of PRP5 stays with U2 snRNA and the acidic loop still occupies the RNA path. The pre-A conformation is specifically stabilized by the splicing factors SF1, DNAJC8 and SF3A2. Cancer-derived mutations in SF3B1 damage its association with PRP5, compromising BS proofreading. Together, these findings reveal key insights into prespliceosome assembly and BS selection or proofreading by PRP5.

PubMed: 38196034
DOI: 10.1038/s41594-023-01188-0

実験手法

ELECTRON MICROSCOPY (2.5 Å)