Induced pluripotency: dissecting the role of ADAR-mediated RNA editing

• Autores: Alejandro Fuentes Iglesias
• Directores de la Tesis: Miguel Angel Fidalgo Pérez (dir. tes.), Anxo Vidal Figueroa (dir. tes.)
• Lectura: En la Universidade de Santiago de Compostela ( España ) en 2023
• Idioma: inglés
• Número de páginas: 266
• Tribunal Calificador de la Tesis: Miguel Antonio López Pérez (presid.), Ana Sevilla Hernández (secret.), Francesca M. Aguiló Payeras (voc.)
• Programa de doctorado: Programa de Doctorado en Medicina Molecular por la Universidad de Santiago de Compostela
• Materias:
  • Ciencias de la vida
    • Biología celular
      • Cultivo celular
    • Genética
• Enlaces
  • Tesis en acceso abierto en: MINERVA
• Resumen

  • 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.