Epitranscriptomics & Ageing (EpiAgeing)
Cellular identity is tightly regulated by chromatin and DNA modifications (Epigenetics), ensuring critical processes such as proper embryonic development or adequate tissue homeostasis. Although RNA chemical modifications (Epitranscriptomics) are intricately linked to the structural and functional diversity of the transcriptome, their contribution to cellular identity and plasticity remains incompletely understood. In our lab we are interested in deciphering epigenetic and epitranscriptomic patterns and dynamics which are key to regulate cell identity and plasticity. We aim at dissecting new pathways involved in the loss of molecular fidelity observed during ageing and in ageing-related disorders. Moreover, given the reversible nature of these modifications, we are interested in identifying druggable epitranscriptomic targets that could be very valuable for clinical applications.
Research Lines
- Epitranscriptomics and agein.
- Epitranscriptomics and ageing crosstalk.
- Pluripotency and reprogramming.
- Transposable element regulation in pluripotency, reprogramming and ageing.
Members
Selected publications
Epitranscriptomics: new players in an old game.
An Optimized Immunoprecipitation Protocol for Assessing Protein-RNA Interactions In Vitro.
ADAR1-Dependent RNA Editing Promotes MET and iPSC Reprogramming by Alleviating ER Stress
BMAL1 coordinates energy metabolism and differentiation of pluripotent stem cells
Selected Results
Figure 1. Conservation of the known RNA chemical modifications in archaea, bacteria end eukarya.
Figure 2. Cartoon of the epigenetic (i.e. histones and DNA) and epitranscriptomic (i.e. RNA) regulation of cell identity.
Figure 3. ERV regulation by recruiting epigenetic complexes to chromatin in ESCs through RNA. Repression of MERVL loci through RNA-dependent recruitment of TET2/PSPC1 for post-transcriptional regulation by hm5C deposition, coordinated with epigenetic repression by HDAC1/2-mediated deacetylation. Guallar et al, Nature Genetics 2018.
Figure 4. RNA editing by ADAR1 safeguards mesenchymal-to-epithelial transition during reprogramming. ADAR1 orchestrates cell fate decisions by limiting MDA5 sensing of double-strand containing RNAs encoding membrane proteins and, by doing so, influences the balance between ER stress/UPR and innate immune response to promote somatic cell reprogramming. Guallar and Fuentes-Iglesias et al, Cell Stem Cell 2020.