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Regulação do RNA e envelhecimento

Aging is characterized by a progressive decline in cellular homeostasis and stands as the single most significant risk factor for many prevalent human diseases. At the heart of cellular homeostasis is the cell's ability to control gene expression, which entails the production of the RNAs and proteins required for proper cellular function. This process is exceptionally complex and prone to age-related malfunction.

Crucial steps in gene expression regulation are elicited at the RNA level by RNA-binding proteins (RBPs). There is mounting evidence suggesting that the expression, solubility, or activity of many RBPs are compromised in the tissues of elderly individuals. However, the extent and functional implications of these changes remain poorly understood. Our primary objective is to delve into how RBP malfunction and disruptions in RNA regulatory processes contribute to the aging process, and to utilise this knowledge to develop novel therapies aimed at promoting healthspan.

Equipa de Investigação

Carlos Custódia
Lab Manager
carloscustodia@medicina.ulisboa.pt

André Balsinha
MSc Student
abalsinha@medicina.ulisboa.pt

Áreas de Investigação

  • Biologia molecular e bioquímica
  • Biologia do RNA
  • Regulação de genes
  • Envelhecimento

Prémios

2012 Bolsa de estudo da Cold Spring Harbor Laboratory, EUA

2010-2012 Prémio Cardini, Fundación Instituto Leloir, Argentina

2010 Prémio Melhor Poster na 5th International Meeting of the Latin American Society for Developmental Biology, Chile

2010 Bolsa de estudo Keystone Symposia, EUA

Publicações Selecionadas

Perez-Perri JI, Ferring-Appel D, Huppertz I, Schwarzl T, Sahadevan S, Stein F, Rettel M, Galy B, Hentze MW (2023). The RNA-binding protein landscapes differ between mammalian organs and cultured cells. Nature Commun. 14(1):2074. doi: 10.1038/s41467-023-37494-w.

Huppertz I, Perez-Perri JI, Mantas P, Sekaran T, Schwarzl T, Dimitrova-Paternoga L, Hennig A, Neveau PA, Hentze MW (2022). RNA regulates Glycolysis and Embryonic Stem Cell Differentiation via Enolase 1. Mol Cell. S1097-2765(22)00486-5. doi: 10.1016/j.molcel.2022.05.019.

Perez-Perri JI, Noerenberg M, Kamel W, Lenz C, Mohammed S, Hentze MW, Castello A (2021). Global analysis of RNA-binding protein dynamics by comparative and enhanced RNA interactome capture. Nature Protoc. 16(1):27-60. doi: 10.1038/s41596-020-00404-1.

Backlund M, Stein F, Rettel M, Schwarzl T, Perez-Perri JI, Brosig A, Zhou Y, Neu-Yilik G, Hentze MW, Kulozik AE (2020). Plasticity of nuclear and cytoplasmic stress responses of RNA-binding proteins. Nucleic Acids Res. 48(9):4725-4740.

Perez-Perri JI, Rogell B, Schwarzl T, Stein F, Zhou Y, Rettel M, Brosig A, Hentze MW (2018). Discovery of RNA-binding proteins and characterization of their dynamic responses by enhanced RNA interactome capture. Nature Commun. 9(1):4408.

Melani M, Valko A, Romero NM, Aguilera MO, Acevedo JM, Bhujabal Z, Perez-Perri J, de la Riva-Carrasco RV, Katz MJ, Sorianello E, D'Alessio C, Juhász G, Johansen T, Colombo MI, Wappner P (2017). Zonda is a novel early component of the autophagy pathway in Drosophila. Mol Biol Cell. 28(22):3070-3081.

Perez-Perri JI, Dengler VL, Audetat KA, Pandey A, Bonner EA, Urh M, Mendez J, Daniels DL, Wappner P, Galbraith MD, Espinosa JM (2016). The TIP60 Complex Is a Conserved Coactivator of HIF1A. Cell Rep. 16(1):37-47.

Perez-Perri JI, Acevedo JM and Wappner P (2011). Epigenetics: New Questions on the Response to Hypoxia. Review. Int J Mol Sci. 12(7).

Dekanty A, Romero NM, Bertolin AP, Thomas MG, Leishman CC, Perez-Perri JI, Bocaccio GL and Wappner P (2010). Drosophila Genome-Wide RNAi Screen Identifies Multiple Regulators of HIF–Dependent Transcription in Hypoxia. PLoS Genet. 6(6).

group leader : Joel Perez-Perri
Saiba Mais
  • Investigador Principal iMM desde 2023
  • Research Staff Scientist, EMBL, Heidelberg, Alemanha (2020-2023)
  • Pós-Doutoramento, EMBL, Heidelberg, Alemanha (2014-2020)
  • Doutoramento em Genética Fisiologia Molecular, Fundación Instituto Leloir e Universidad de Buenos Aires, Argentina (2013)