Origin and evolution of neural microexons
Post-transcriptional networks control multiple aspects of neuronal biology and their deregulation has been associated with human neurological disorders. This thesis focuses on regulation at the level of pre-mRNA splicing, particularly on a recently described programme of neural microexons implicated...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2020 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/668750 |
| Acceso en línea: | http://hdl.handle.net/10803/668750 |
| Access Level: | acceso abierto |
| Palabra clave: | Evolution Neuron RNA Splicing Microexons Evolución Neurona Microexones 616.8 |
| Sumario: | Post-transcriptional networks control multiple aspects of neuronal biology and their deregulation has been associated with human neurological disorders. This thesis focuses on regulation at the level of pre-mRNA splicing, particularly on a recently described programme of neural microexons implicated in autism. In the search for the evolutionary origins of this splicing programme we discovered neural microexons in non-vertebrate animals and a novel protein domain responsible for their regulation, the ‘enhancer of microexons’ or eMIC domain. This domain represents a neofunctionalization of an ancestral splicing factor that originated and was restricted to the neural system in bilaterian ancestors. We provide biochemical evidence for a role of the eMIC domain in 3’ splice site recognition, and profile the regulatory features associated with its mode of splicing regulation in the fruitfly Drosophila melanogaster. Ongoing experiments with loss- and gain-of-function flies for the eMIC domain are unravelling how the microexon programme evolved to control fundamental aspects of neuronal biology in animals. |
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