Structural basis of branch site recognition by the human spliceosome

• Verfasst von: Tholen, Jonas [VerfasserIn]
• Verfasst von: Razew, Michal [VerfasserIn]
• Verfasst von: Weis, Felix [VerfasserIn]
• Verfasst von: Galej, Wojciech P. [VerfasserIn]
• Titel: Structural basis of branch site recognition by the human spliceosome
• Verf.angabe: Jonas Tholen, Michal Razew, Felix Weis, Wojciech P. Galej
• Jahr: 2022
• Umfang: 7 S.
• Fussnoten: Published online 25 November 2021 ; Gesehen am 23.03.2022
• Titel Quelle: Enthalten in: Science
• Ort Quelle: Washington, DC [u.a.] : American Association for the Advancement of Science, 1880
• Jahr Quelle: 2022
• Band/Heft Quelle: 375(2022), 6576 vom: Jan., Seite 50-57
• ISSN Quelle: 1095-9203
• DOI: doi:10.1126/science.abm4245
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1796380822

Abstract

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 17S 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.