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Precision Medicine

Epitranscriptomics & Ageing (EpiAgeing)

Diana Guallar
Group Leader | Ramón y Cajal Researcher
diana.guallar@usc.es
 
Lab: P1L3
Field of knowledge

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

Alejandro Fuentes Iglesias
Research associate
alejandro.fuentes@usc.es

 

Cristina De La Parte Rodríguez
Xunta de Galicia fellowship
Alba Cortés Coego
Xunta de Galicia fellowship
Lucía Ramos Lage
PhD student

Selected publications

Epitranscriptomics: new players in an old game.

Coego A, Covelo-Molares H, Guallar D.
Biochemical Society Transactions (2023) 0 1 -14.

An Optimized Immunoprecipitation Protocol for Assessing Protein-RNA Interactions In Vitro.

Fuentes-Iglesias A, Garcia-Outeiral V, Pardavila JA, Wang J, Fidalgo M, Guallar D.

ADAR1-Dependent RNA Editing Promotes MET and iPSC Reprogramming by Alleviating ER Stress

Diana Guallar, Alejandro Fuentes-Iglesias, Yara Souto, Cristina Ameneiro, Oscar Freire-Agulleiro, Jose Angel Pardavila, Adriana Escudero, Vera Garcia-Outeiral, Tiago Moreira, Carmen Saenz, Heng Xiong, Dongbing Liu, Shidi Xiao, Yong Hou, Kui Wu, Daniel Torrecilla, Jochen C. Hartner, Miguel G. Blanco, Leo J. Lee, Miguel López, Carl R. Walkley, Jianlong Wang, Miguel Fidalgo.

BMAL1 coordinates energy metabolism and differentiation of pluripotent stem cells

Ameneiro, Cristina; Moreira, Tiago; Fuentes-Iglesias, Alejandro; Coego, Alba; Garcia-Outeiral, Vera; Escudero, Adriana; Torrecilla, Daniel; Mulero-Navarro, Sonia; Carvajal-Gonzalez, Jose Maria; Guallar, Diana; Fidalgo, Miguel
RNA-dependent chromatin targeting of TET2 for endogenous retrovirus control in pluripotent stem cells
Guallar, Diana; Bi, Xianju; Pardavila, Jose Angel; Huang, Xin; Saenz, Carmen; Shi, Xianle; Zhou, Hongwei; Faiola, Francesco; Ding, Junjun; Haruehanroengra, Phensinee; Yang, Fan; Li, Dan; Sanchez-Priego, Carlos; Saunders, Arven; Pan, Feng; Valdes, Victor Julian; Kelley, Kevin; Blanco, Miguel G.; Chen, Lingyi; Wang, Huayan; Sheng, Jia; Xu, Mingjiang; Fidalgo, Miguel; Shen, Xiaohua; Wang, Jianlong

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.

Projects

National project(s)

Analysis of New Regulators of Pluripotency
REF: ED431F 2022/011Duration: -
PI: Diana Guallar
Dissecting epigenetic and epitranscriptomic regulation of ageing and age-associated disorders.
REF: RYC2019-027305-IDuration: -
PI: Diana Guallar
Diseccionar la regulación epigenética y epitranscriptómica del envejecimiento y las enfermedades ...
REF: RYC2019-027305-IDuration: -
PI: Diana Guallar Artal
AGENCIA ESTATAL DE INVESTIGACION