8P25

Solution structure of a chimeric U2AF2 RRM2 / FUBP1 N-Box

8P25 の概要

• エントリーDOI: 10.2210/pdb8p25/pdb
• NMR情報: BMRB: 34816
• 分子名称: Splicing factor U2AF 65 kDa subunit,Far upstream element-binding protein 1 (1 entity in total)
• 機能のキーワード: splicing, regulation, protein-protein interaction, rrm
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 16296.17

構造登録者

Hipp, C.,Sattler, M. (登録日: 2023-05-14, 公開日: 2023-07-26, 最終更新日: 2024-06-19)

主引用文献

Ebersberger, S.,Hipp, C.,Mulorz, M.M.,Buchbender, A.,Hubrich, D.,Kang, H.S.,Martinez-Lumbreras, S.,Kristofori, P.,Sutandy, F.X.R.,Llacsahuanga Allcca, L.,Schonfeld, J.,Bakisoglu, C.,Busch, A.,Hanel, H.,Tretow, K.,Welzel, M.,Di Liddo, A.,Mockel, M.M.,Zarnack, K.,Ebersberger, I.,Legewie, S.,Luck, K.,Sattler, M.,Konig, J.
FUBP1 is a general splicing factor facilitating 3' splice site recognition and splicing of long introns.
Mol.Cell, 83:2653-, 2023

PubMed Abstract: Splicing of pre-mRNAs critically contributes to gene regulation and proteome expansion in eukaryotes, but our understanding of the recognition and pairing of splice sites during spliceosome assembly lacks detail. Here, we identify the multidomain RNA-binding protein FUBP1 as a key splicing factor that binds to a hitherto unknown cis-regulatory motif. By collecting NMR, structural, and in vivo interaction data, we demonstrate that FUBP1 stabilizes U2AF2 and SF1, key components at the 3' splice site, through multivalent binding interfaces located within its disordered regions. Transcriptional profiling and kinetic modeling reveal that FUBP1 is required for efficient splicing of long introns, which is impaired in cancer patients harboring FUBP1 mutations. Notably, FUBP1 interacts with numerous U1 snRNP-associated proteins, suggesting a unique role for FUBP1 in splice site bridging for long introns. We propose a compelling model for 3' splice site recognition of long introns, which represent 80% of all human introns.

PubMed: 37506698
DOI: 10.1016/j.molcel.2023.07.002

実験手法

SOLUTION NMR