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 three 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.

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)

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Group news & mentions

1 Jun 2014

Reportaje sobre las principales estrategias que están desarrollando científicos españoles de primera línia mundial para encontrar nuevas fórmulas terapéuticas contra el cáncer.

16 Feb 2014

El periodista de La Vanguardia Josep Corbella entrevista al investigador del IRB 

26 Jan 2014

El concurso "La Vanguardia de la ciencia" organizado por el periódico La Vanguardia y la Fundación Catalunya - La Pedrera ha elegido una investigación de

15 Oct 2013

Eulàlia Belloc, investigadora asociada en el grupo de

Upcoming events

07 Jan

Speaker: Francisco Freixo, PhD Student, IRB Barcelona, Spain

 

07 Jan

Speaker: Francisco Freixo, PhD Student, IRB Barcelona, Spain

 

09 Jan

Speaker: Dr.Eduard Batlle,

ICREA Research professor, Group Leader Colorectal Cancer Lab, Oncology Programme Head- IRB Barcelona, Spain

22 Jan

Speaker: Ernst Lengyel,

MD PhD- Chairman, Department of Obstetrics and Gynecology- Arthur L. and Lee G. Herbst Professor of Obstetrics and Gymecology- University of Chicago Medicine (USA)

 

Funding

  • 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)