Structural basis of branch site recognition by the human spliceosome
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 huma...
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| Main Authors: | , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2022
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| In: |
Science
Year: 2022, Volume: 375, Issue: 6576, Pages: 50-57 |
| ISSN: | 1095-9203 |
| DOI: | 10.1126/science.abm4245 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1126/science.abm4245 Verlag, lizenzpflichtig, Volltext: https://www.science.org/doi/10.1126/science.abm4245 
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| Author Notes: | Jonas Tholen, Michal Razew, Felix Weis, Wojciech P. Galej |
| Summary: | 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. |
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| Item Description: | Published online 25 November 2021 Gesehen am 23.03.2022 |
| Physical Description: | Online Resource |
| ISSN: | 1095-9203 |
| DOI: | 10.1126/science.abm4245 |