Molecular mechanisms of alternative splicing regulation by antitumor drugs targeting U2 snRNP
RNA splicing is the process of removal of introns from pre-mRNAs. It is carried out by the spliceosome, composed of five small nuclear ribonucleoproteins (snRNPs). Several small molecules with antitumor properties target SF3B1, a U2 snRNP component frequently mutated in cancer that helps U2 snRNP re...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2016 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/525840 |
| Acceso en línea: | http://hdl.handle.net/10803/525840 |
| Access Level: | acceso abierto |
| Palabra clave: | Alternative splicing Antitumor drugs SF3B1 Spliceosome U2 snRNP Splicing alternativo Fármacos antitumorales 577 |
| Sumario: | RNA splicing is the process of removal of introns from pre-mRNAs. It is carried out by the spliceosome, composed of five small nuclear ribonucleoproteins (snRNPs). Several small molecules with antitumor properties target SF3B1, a U2 snRNP component frequently mutated in cancer that helps U2 snRNP recruitment to branch point (BP) sequences required for splicing catalysis. Together with collaborators from the University of Barcelona, we describe a new drug variant with improved splicing inhibitory and antiproliferative activities, as well as the novel concept of drug-antisense oligonucleotide conjugates. We report that 3' splice site sensitivity to drugs is finely tuned by transcripts’ sequence content. We also show that different drug variants display both similarities and differences in alternative splicing modulation. |
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