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キーワード
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Structure paper

タイトル	Structural basis of branch site recognition by the human spliceosome.
ジャーナル・号・ページ	Science, Vol. 375, Issue 6576, Page 50-57, Year 2022
掲載日	2022年1月7日
著者	Jonas Tholen / Michal Razew / Felix Weis / Wojciech P Galej /
PubMed 要旨	Recognition of the intron branch site (BS) by the U2 small nuclear ribonucleoprotein (snRNP) is a critical event during spliceosome assembly. In mammals, BS sequences are poorly conserved, and ...Recognition of the intron branch site (BS) by the U2 small nuclear ribonucleoprotein (snRNP) is a critical event during spliceosome assembly. In mammals, BS sequences are poorly conserved, and unambiguous intron recognition cannot be achieved solely through a base-pairing mechanism. We isolated human 17 U2 snRNP and reconstituted in vitro its adenosine 5´-triphosphate (ATP)–dependent remodeling and binding to the pre–messenger RNA substrate. We determined a series of high-resolution (2.0 to 2.2 angstrom) structures providing snapshots of the BS selection process. The substrate-bound U2 snRNP shows that SF3B6 stabilizes the BS:U2 snRNA duplex, which could aid binding of introns with poor sequence complementarity. ATP-dependent remodeling uncoupled from substrate binding captures U2 snRNA in a conformation that competes with BS recognition, providing a selection mechanism based on branch helix stability.
リンク	Science / PubMed:34822310 / PubMed Central
手法	EM (単粒子)
解像度	2.05 - 3.3 Å
構造データ	13793 7q3l EMDB-13793: Human 17S U2 snRNP 5' domain core PDB-7q3l: Human 17S U2 snRNP 5' domain 手法: EM (単粒子) / 解像度: 2.21 Å EMDB-13810: Human 17S U2 snRNP HEAT repeats 手法: EM (単粒子) / 解像度: 2.9 Å 13811 7q4o EMDB-13811, PDB-7q4o: Substrate-bound A-like U2 snRNP 手法: EM (単粒子) / 解像度: 2.1 Å 13812 7q4p EMDB-13812, PDB-7q4p: U2 snRNP after ATP-dependent remodelling 手法: EM (単粒子) / 解像度: 2.15 Å EMDB-13813: A-like U2 snRNP medium-resolution map 手法: EM (単粒子) / 解像度: 2.6 Å EMDB-13814: AMP-PCP-treated A-like U2 snRNP 手法: EM (単粒子) / 解像度: 3.3 Å EMDB-13815: U2 snRNP 5' domain high resolution map 手法: EM (単粒子) / 解像度: 2.05 Å
化合物	ChemComp-ZN: Unknown entry ChemComp-HOH: WATER / 水
由来	homo sapiens (ヒト) human (ヒト) synthetic construct (人工物)
キーワード	NUCLEAR PROTEIN / snRNP (核内低分子リボ核タンパク質) / Spliceosome (スプライセオソーム) / U2 snRNP / Splicing