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The anti-tumor drug E7107 reveals an essential role for SF3b in remodeling U2 snRNP to expose the branch point-binding region
Open accessAbstract
Duplex formation between the branch point-binding region (BBR) of U2 snRNA and the branch point sequence (BPS) in the intron is essential for splicing. Both the BBR and BPS interact with the U2 small nuclear ribonucleoprotein (snRNP)-associated SF3b complex, which is the target of the anti-tumor drug E7107. We show that E7107 blocks spliceosome assembly by preventing tight binding of U2 snRNP to pre-mRNA. E7107 has no apparent effect on U2 snRNP integrity. Instead, E7107 abolishes an ATP-dependent conformational change in U2 snRNP that exposes the BBR. We conclude that SF3b is required for this remodeling, which exposes the BBR for tight U2 snRNP binding to pre-mRNA.
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Cited by
Therapeutic targeting of splicing in cancer
Lee, S. C.-W., & Abdel-Wahab, O. (2016) · Nature Medicine · doi:10.1038/nm.4165 · Cited by 561
Obeng, E. A., Chappell, R. J., Seiler, M., Chen, M. C., Campagna, D. R., Schmidt, P. J., Schneider, R. K., Lord, A. M., Wang, L., Gambe, R. G., et al. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.08.006 · Cited by 380
Structural basis of splicing modulation by antitumor macrolide compounds
Cretu, C., Agrawal, A. A., Cook, A., Will, C. L., Fekkes, P., Smith, P. G., Lührmann, R., Larsen, N., Buonamici, S., & Pena, V. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.03.011 · Cited by 174
Metadata
- Authors
- Folco, E. G., Coil, K. E., & Reed, R.
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2011-03-01
- Volume
- 25
- Issue
- 5
- Pages
- 440-444
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- OpenAlex
- W2109676193
- Cited by
- 162
- References
- 0
- Type
- posted content
- Language
- en
- Open access
- diamond
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- CoChat. (2026). Citation check: The anti-tumor drug E7107 reveals an essential role for SF3b in remodeling U2 snRNP to expose the branch point-binding region. https://app.cochat.ai/papers/10.1101/gad.2009411
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- Folco, E. G., Coil, K. E., & Reed, R. (2011). The anti-tumor drug E7107 reveals an essential role for SF3b in remodeling U2 snRNP to expose the branch point-binding region. Genes & Development. https://doi.org/10.1101/gad.2009411
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