Induced pluripotencydissecting the role of ADAR-mediated RNA editing

  1. Fuentes Iglesias, Alejandro
Dirixida por:
  1. Miguel Angel Fidalgo Pérez Director
  2. Anxo Vidal Figueroa Director

Universidade de defensa: Universidade de Santiago de Compostela

Fecha de defensa: 09 de febreiro de 2023

  1. Miguel Antonio López Pérez Presidente
  2. Ana Sevilla Hernández Secretario/a
  3. Francesca M. Aguiló Payeras Vogal
  1. Departamento de Fisioloxía

Tipo: Tese


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.