Exploring the role of differential expression of splicing factors and regulators in tissue-specific alternative splicing
Alternative splicing (AS) is an important step in the pathway of gene expression and regulation. The splicing process is catalyzed by the Spliceosome, a complex molecular machinery that is dynamically assembled on the pre-mRNA in order to remove introns and ligate together exons. Perturbation of Cor...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2019 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/668015 |
| Acceso en línea: | http://hdl.handle.net/10803/668015 |
| Access Level: | acceso abierto |
| Palabra clave: | Alternative splicing Spliceosome Splicing regulation Genotipe-Tissue Expression (GTEx) project The cancer genome atlas Splicing alternativo Spliceosoma Regulación de splicing Proyecto de expresión de Genotipo-Tejido Atlas de cáncer genómico 575 |
| Sumario: | Alternative splicing (AS) is an important step in the pathway of gene expression and regulation. The splicing process is catalyzed by the Spliceosome, a complex molecular machinery that is dynamically assembled on the pre-mRNA in order to remove introns and ligate together exons. Perturbation of Core Spliceosomal Components (CSCs) -those components which are believed to be essential for intron removal in general- has been shown to affect splice site selection and AS. Little is known about whether this is a physiological mechanism of tissue-specific AS regulation. In this study, we investigate the potential role of CSCs and classical splicing regulators (CSRs) in tissue-specific AS and its variation across human populations by correlating differences in their levels of expression with AS changes across human organs and individuals. Our results recapitulate already known regulatory mechanisms and identify potential novel ones involving both CSRs and CSCs. We identified potential regulators whose gene expression alteration might play a role in human cancers. Moreover we observed that inclusion levels of some specific exons correlated with patient’s survival rate. Understanding the regulatory mechanisms behind will give precious insights on cancer biology and cancer treatment development. |
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