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Mammalian Translation initiation and cellular Growth Control: (a). Translational Regulation of the Transcription Factor ELK-1. (b). Studies on Global Regulation. (c). Translational Profiling of Chromosome 21

English title Mammalian Translation initiation and cellular Growth Control: (a). Translational Regulation of the Transcription Factor ELK-1. (b). Studies on Global Regulation. (c). Translational Profiling of Chromosome 21
Applicant Curran Joseph
Number 116170
Funding scheme Project funding (Div. I-III)
Research institution Dépt Microbiologie et Médecine Moléculaire Faculté de Médecine Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Biochemistry
Start/End 01.04.2007 - 30.11.2010
Approved amount 211'107.00
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All Disciplines (3)

Discipline
Biochemistry
Experimental Cancer Research
Molecular Biology

Keywords (5)

translation initiation; ELK-1; growth regulation; cancer; microarray

Lay Summary (English)

Lead
Lay summary
The expression of mammalian genes is controlled essentially at two levels:
1). Transcription in the nucleus, in which the “hard-copy” genetic information in the form of chromosomal DNA is copied into an intermediate called messenger RNA (mRNA) 2). Translation in the cytoplasm in which the information stored in the RNA intermediate is decoded into protein. Proteins are essential macromolecules for cell growth. They form the structures of the cell and provide enzymes involved in all stages of cellular metabolism. They also serve as the sentinels that respond to cell growth signals. Protein synthesis must therefore be tightly controlled and must be able to respond rapidly to changes in the physiological status of the cell. The importance of this control is highlighted by the fact that perturbations in this regulation are frequently associated with tumours.

Expression of proteins in the cell takes place on a macromolecular machine called the ribosome. At any moment in time these ribosomes are associated with populations of cellular mRNAs. However, these populations change rapidly in response to signals both extracellular (e.g. the binding of a hormone such as insulin), or intracellular (e.g. an intracellular stress induced by heat shock). The aim of our project is to analyse the features in defined cellular mRNAs that couple there association with ribosomes to defined physiological conditions. More long term, we would like to gain insights into how this tightly controlled association becomes perturbed in tumoural cell lines.

A new and exciting observation is that many transcribed RNAs in the human genome do not code for protein. Indeed, greater than 50% of the RNAs made in the cell are “non-coding”. In part of our project we have focused on all the RNAs (both coding and non-coding) transcribed from human chromosome 21 (using a very high resolution analysis). We will examine if the non-coding RNAs also associate with ribosomes, and if the pattern of association shows cell type specificity (a result that might suggest functionality). The aim is to provide evidence that these RNAs, although non-coding, modulate the translation read-out from the ribosome (i.e the nature and quantity of proteins expressed). We also aim to examine if the association of these RNAs responds to drugs that perturb translation.

These studies should provide new insights into the link between cell growth control and protein expression. The high resolution studies may also provide new targets for anti-cancer therapy.
Direct link to Lay Summary Last update: 21.02.2013

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Associated projects

Number Title Start Funding scheme
143772 The elk-1 gene: A model for how alternative splicing in the 5'UTR can modulate translational reinitiation in mammalian cells. 01.10.2012 Project funding (Div. I-III)

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