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 www.gallegolab.org)
1)A comparative analysis of Multisubunit Tethering Complexes
2)Characterize the interplay between the transport of vesicles and mRNA localization

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"

     

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Group news & mentions

20 Mar 2017

The 2017 Issue of the European Biotechnology magazine on the Life Sciences and Industry features recent studies conducted at IRB Barcelona by Oriol Gallego, research associate with the Translationa

<p>Left, atomic structure of RNA polymerase I in its inactive form - homodimer; Right, atomic structure of RNA polymerase I in its active form -heterodimer with Rrn3-. (Carlos Fernández-Tornero CIB/CSIC and Oriol Gallego, IRB Barcelona)</p>
17 Mar 2017

The local newspaper “Diari de Girona” publishes an article about the discovery of a mechanism responsible for halting protein synthesis when cells are deprived of nutrients.

<p>Left, atomic structure of RNA polymerase I in its inactive form - homodimer; Right, atomic structure of RNA polymerase I in its active form -heterodimer with Rrn3-. (Carlos Fernández-Tornero CIB/CSIC and Oriol Gallego, IRB Barcelona)</p>
16 Mar 2017

Researchers at the Consejo Superior de Investigaciones Científicas (CSIC) in Madrid and Salamanca and at the Institute for Research in Biomedicine (IRB Barcelona) have unveiled one of the

<p>The image shows tumour cells infected by the virus, which expresses a fluorescent protein. Over the days (in the image fifth day), the virus multiplies, generating new virions that infect more cancer cells (IDIBAPS, IRB Barcelona)</p>
16 Mar 2017

Scientists at the IDIBAPS Biomedical Research Institute and at the Institute for Research in Biomedicine (IRB Barcelona) lead a study in which they have designed a new strategy to achieve genetical

Upcoming events

28 Mar
IRB Meeting Room 1 – IRB Administration Building 1st Floor
Speaker:
Speaker: Albert Farré, Brand Manager at Novartis Oncology
29 Mar
Aula Fèlix Serratosa, Parc Científic de Barcelona
Speaker:
Iracema Caballero, IBMB-CSIC
29 Mar
Aula Fèlix Serratosa, Parc Científic de Barcelona
Speaker:
Javier López-Rios, PhD Development and Evolution, Department of Biomedicine, University of Basel, Switzerland