Molecular MedicineTranslational control of cell cycle and differentiation

Translational control of cell cycle and differentiation

Recent years have seen a paradigm shift in our understanding of gene activity and regulation. It is now clear that processing of primary transcripts as well as translational control open a myriad of opportunities for gene regulation, which are extensively used in virtually every human gene. However, how these events are regulated and how alterations of these finely tuned processes contribute to physio/pathological processes is not yet well understood.

The primary interest of our group has been to understand the molecular mechanisms that dictate alternative 3’ UTR formation and the temporal and spatial translational control of specific mRNAs during cell cycle progression and chromosome segregation, senescence and related pathologies. Cell cycle progression is programmed, at least in part, by stored silent mRNAs. These mRNAs are not translated en masse at any one time, or even at any one place; rather, their translation is specifically regulated by sequences located at their 3´-untranslated regions (3´-UTRs) and their binding proteins.

Our work focuses on four main lines of research:

First, to elucidate the mechanisms underlying the translational control by cytoplasmic polyadenylation cis-acting elements and trans-acting factors:
1) Genome-wide identification of the mRNAs that are regulated by nuclear and cytoplasmic changes in their poly(A) tail length;
2) Determination of the configuration of cis-acting elements that define the temporal and spatial translational regulation;
3) Functional and structural characterization of the ribonucleoprotein (RNPs) complexes that mediate this translational regulation.

Second, to obtain insights in how this translational control circuit regulates cell cycle progression by establishing a molecular circuit, stabilized by positive and negative feed-back loops to generate an irreversible self sustain hysteric system with molecular memory and switch-like phase transitions.

Third, to explore the role of these mRNA processing and translation mechanisms in the reprogramming of gene expression in tumoral events and angiogenesis and the development of tools with prognostic and therapeutic value.

Forth, to study the symmetric distribution of cellular components (research directed by Oriol Gallego, see
1)A comparative analysis of Multisubunit Tethering Complexes
2)Characterize the interplay between the transport of vesicles and mRNA localization

Villanueva E, Navarro P, Rovira-Rigau M, Sibilio A, Méndez R and Fillat C.
Nat Commun, 8 14833 (2017)
Maillo C, Martín J, Sebastián D, Hernández-Alvarez M, García-Rocha M, Reina O, Zorzano A, Fernandez M and Méndez R.
Nat Cell Biol, 19 (2), 94-105 (2017)
Calderone V, Gallego J, Fernandez-Miranda G, Garcia-Pras E, Maillo C, Berzigotti A, Mejias M, Bava FA, Angulo-Urarte A, Graupera M, Navarro P, Bosch J, Fernandez M and Mendez R.
Gastroenterology, 150 (4), 982-97.e30 (2016)
Bava FA, Eliscovich C, Ferreira PG, Miñana B, Ben-Dov C, Guigó R, Valcárcel J and Méndez R.
Nature, 495 (7439), 121-5 (2013)
Weill L, Belloc E, Bava FA and Méndez R.
Nat Struct Mol Biol, 19 (6), 577-85 (2012)
Fernández-Miranda G and Méndez R.
Ageing Res Rev, 11 (4), 460-72 (2012)
Ortiz-Zapater E, Pineda D, Martínez-Bosch N, Fernández-Miranda G, Iglesias M, Alameda F, Moreno M, Eliscovich C, Eyras E, Real FX, Méndez R and Navarro P.
Nat Med, 18 (1), 83-90 (2011)

  • AICR (Association for International Cancer Research)
  • ICREA (Catalan Institute of Research and Advanced Studies)
  • Ministerio de Ciencia e Innovación (Spanish Ministry of Science and Innovation)
  • AGAUR (Agència de Gestió d’Ajuts Universitaris i de Recerca)
  • Ministerio de Economía y Competitividad (MINECO)
  • European Commission (EC), Fondo Europeo de Desarrollo Regional (FEDER), "Una manera de hacer Europa"



Group news & mentions

<p>Gonzalo Fernández-Miranda, Project Leader and associate researcher with the Translational Control of Cell Cycle and Differentiation Lab. Image: CaixaImpulse.</p>
20 Jul 2017

The third edition of the CaixaImpulse, a programme run by the Banking Foundation La Caixa and Caixa Capital Risc that supports the development of bio-health projects, is to fund an immunotherapy pr

<p>The experiments have been carried out using Xenopus laevis oocytes, an animal model used by the laboratory to study fundamental processes involved in gene regulation. Image: microscopy, Eulàlia Belloc.</p>
18 Jul 2017

Translation regulation—the process by which the amount of protein synthesized from its messenger RNA (mRNA) is controlled—is a crucial step in establishing the degree of gene expression during even

27 Apr 2017

"Saber Vivir" magazine dedicates an article to a study—co-led by Cristina Fillat, head of the Gene Therapy and Cancer Group at IDIBAPS, and Raúl Méndez, ICREA researcher at IRB Barcelona—on an inno

14 Apr 2017

La Sexta newscast team has covered the research performed by IDIBAPS

Upcoming events

20 Sep
Auditorium, Parc Científic de Barcelona
Speaker: Isabel Almudi, Ph.D. Developmental Biology, Evolutionary Biology Andalusian Center for Developmental Biology, Sevilla, Spain.
13 Nov - 15 Nov
Institut d'Estudis Catalans (IEC), Barcelona
Modesto Orozco, Marc Martí-Renom, Giacomo Cavalli
15 Nov - 17 Nov
Place: Palauet Casades, carrer de Mallorca 283, Barcelona (Spain)