Regulation of NUMB alternative splicing by RBM10 and control of cancer cell proliferation
Alternative pre-mRNA splicing of the Notch regulator NUMB exon 9 switches between isoforms that promote (exon inclusion) or prevent (exon skipping) cell proliferation. We have studied NUMB alternative splicing regulation by RBM10, an RNA binding protein frequently utated in lung adenocarcinomas. The...
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| Formato: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2016 |
| País: | España |
| Recursos: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/458766 |
| Acesso em linha: | http://hdl.handle.net/10803/458766 |
| Access Level: | acceso abierto |
| Palavra-chave: | RBM10 NUMB Lung Cancer Càncer de pulmó Alternative splicing Empalmament alternatiu 577 |
| Resumo: | Alternative pre-mRNA splicing of the Notch regulator NUMB exon 9 switches between isoforms that promote (exon inclusion) or prevent (exon skipping) cell proliferation. We have studied NUMB alternative splicing regulation by RBM10, an RNA binding protein frequently utated in lung adenocarcinomas. The study of cancer-associated BM10 variants revealed domains and residues important for RBM10 function. Structure-function analysis identified residues in RRM2 that, without compromising RNA binding, fail to regulate NUMB exon 9. Immunoprecipitation and mass spectrometry analyses revealed interactors that include U2 snRNP and PRP19 spliceosomal components, allowing us to propose a mechanism for 3' splice site repression by RBM10. |
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