Mechanisms of Disease 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
- 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"