Induced pluripotency: dissecting the role of ADAR-mediated RNA editing
Whereas RNA editing of adenosine-to-inosine (A-to-I) catalyzed by ADAR proteins is intricately linked to transcriptome structural and functional diversity, how this RNA chemical modification contributes to overriding somatic cell identity during reprogramming to pluripotency is largely unexplored. H...
| Autor: | |
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| Tipo de recurso: | tesis doctoral |
| Fecha de publicación: | 2023 |
| País: | España |
| Institución: | Universidad de Santiago de Compostela (USC) |
| Repositorio: | Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela |
| Idioma: | inglés |
| OAI Identifier: | oai:minerva.usc.gal:10347/30317 |
| Acceso en línea: | http://hdl.handle.net/10347/30317 |
| Access Level: | acceso abierto |
| Palabra clave: | Materias::Investigación::24 Ciencias de la vida::2407 Biología celular::240701 Cultivo celular Materias::Investigación::24 Ciencias de la vida::2407 Biología celular::240799 Otras (Reprogramación somática) Materias::Investigación::24 Ciencias de la vida::2409 Genética::240999 Otras (Modificaciones de ARN) |
| Sumario: | Whereas RNA editing of adenosine-to-inosine (A-to-I) catalyzed by ADAR proteins is intricately linked to transcriptome structural and functional diversity, how this RNA chemical modification contributes to overriding somatic cell identity during reprogramming to pluripotency is largely unexplored. Here, I show that the absence of ADAR1-mediated A-to-I editing hampers mesenchymal-to-epithelial transition and impedes the acquisition of pluripotency. Mechanistically, my data reveals that lack of A-to-I editing induces aberrant innate immune response programs through double-stranded sensor MDA5, unleashing endoplasmic reticulum stress and hindering epithelial fate acquisition. Thus, this study establishes a critical role for A-to-I RNA modification in cell fate transitions during reprogramming and opens new avenues for exploring the involvement of ADAR1 in health and disease. |
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