CELLULAR IRESES
Mechanism of cellular IRESes translation
| Coordinatore | EUROPEAN MOLECULAR BIOLOGY LABORATORY
Organization address
address: Meyerhofstrasse 1 contact info |
| Nazionalità Coordinatore | Germany [DE] |
| Totale costo | 0 € |
| EC contributo | 162˙130 € |
| Programma | FP7-PEOPLE
Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) |
| Code Call | FP7-PEOPLE-IIF-2008 |
| Funding Scheme | MC-IIF |
| Anno di inizio | 2009 |
| Periodo (anno-mese-giorno) | 2009-08-01 - 2011-07-31 |
Partecipanti
| # | ||||
|---|---|---|---|---|
| 1 |
EUROPEAN MOLECULAR BIOLOGY LABORATORY
Organization address
address: Meyerhofstrasse 1 contact info |
DE (HEIDELBERG) | coordinator | 162˙130.94 |
Mappa
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Obiettivo del progetto (Objective)
'The central importance of translation control in cancer is just beginning to be fully appreciated. Translation normally initiates with the recruitment of the initiation factors to the 5’ cap of the mRNA for ribosome binding. Curiously, some normally capped cellular messages, which are involved in cell-cycle control, growth and apoptosis, rely alternatively on an internal ribosome entry site (IRES) at their 5’ end and the 3’ poly(A) tail to support translation. The advantage conferred by the IRES is obvious during shutdown of cap-dependent translation: these mRNAs remain bound to the polysomes and maintain steady expression. The deregulation of such mRNAs is directly implicated in tumorigenesis and clearly links translation to cancer. The precise mechanism of translation via cellular IRES and its regulation, the structural/sequence consensus, and its use remain largely unexplored. Here, using the pro-oncogenic c-myc IRES as model, we propose to investigate the role of the 3’poly(A) tail and the possible involvement of distinct set of regulatory factors for the IRES activity, which does not require the canonical poly(A) tail partner, PABP. We will use innovative functional proteomic approaches, which include capturing the RNP complex formed during ribosomal recruitment, and the establishment of high throughput siRNA-based in vivo and in vitro screening assays. Upon completion of the project, we will have a functional understanding of how the poly(A) tail enhances ribosome recruitment in a non-canonical fashion. These results will enable us to gain insight on mechanistic details of translation control. This research will contribute in EU excellence and competitiveness by covering a key area of basic biological process with a strong interest for Europe for its clear relevance to human diseases. It will raise the potential avenue for novel therapeutic strategies against translation and thus hold great promises to turn the research into useful valuable innovation.'
Introduzione (Teaser)
How proteins are translated from messenger RNA (mRNA) is perhaps the very basis of cellular processes. A European research team has focused on one particular means of translation thought to be involved in tumourigenesis.