Exploring the role of DYRK1A in RNA polymerase III transcription : DYRK1A as a potential regulator of TFIIIC
The kinase DYRK1A (dual-specificity tyrosine-regulated kinase 1A) is a dosage-sensitive gene, since both haploinsufficiency and overexpression when in trisomy lead to pathological phenotypes in humans. In this Thesis, the possible role of DYRK1A in regulating RNA polymerase III transcription has bee...
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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:10803/668274 |
| Acceso en línea: | http://hdl.handle.net/10803/668274 |
| Access Level: | acceso abierto |
| Palabra clave: | DYRK1A RNA polymerase III TFIIIC tRNA Phosphorylation Fosforilación Polimerasa 577 |
| Sumario: | The kinase DYRK1A (dual-specificity tyrosine-regulated kinase 1A) is a dosage-sensitive gene, since both haploinsufficiency and overexpression when in trisomy lead to pathological phenotypes in humans. In this Thesis, the possible role of DYRK1A in regulating RNA polymerase III transcription has been explored. The results show that DYRK1A is recruited to RNA polymerase III-bound tRNA genes (tDNAs) in multiple human cell lines. In addition, the tDNAs are occupied by the RNA polymerase III basal transcription factor TFIIIC. DYRK1A is shown to not only interact with TFIIIC but to phosphorylate several subunits of the TFIIIC complex in vitro. Indeed, inhibition of the DYRK1A catalytic activity results in reduction of the recruitment of TFIIIC to tDNAs. These results point to DYRK1A as a novel kinase of the TFIIIC complex, the first described in mammals, and allows to propose DYRK1A as a potential novel regulator of RNA polymerase III transcription by acting on TFIIIC. |
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