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Nucleic Acids Research Advance Access published online on June 25, 2007
Nucleic Acids Research, doi:10.1093/nar/gkm482
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© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Molecular Biology

Alternatively spliced isoforms of the human elk-1 mRNA within the 5' UTR: implications for ELK-1 expression

Tanguy Araud, Raphael Genolet, Pascale Jaquier-Gubler and Joseph Curran*

Department of Microbiology and Molecular Medicine, University of Geneva Medical School (CMU), 1 rue Michel Servet, CH-1211 Geneva, Switzerland

*To whom correspondence should be addressed. Tel: +0041 22 3795799; Fax: +0041 22 3795702; Email: Joseph.Curran{at}medecine.unige.ch

Received January 9, 2007. Revised June 1, 2007. Accepted June 4, 2007.

The expression of cellular proteins that play central roles in the regulation of cell growth and differentiation is frequently tightly controlled at the level of translation initiation. In this article, we provide evidence that the ETS domain transcription factor ELK-1 forms part of this class of genes. Its mRNA 5' UTR is composed of a complexed mosaic of elements, including uAUGs, uORFs and RNA structure, that interplay to modulate ribosomal access to the ELK-1 AUG start codon. Superimposed upon this is the generation of two different 5' UTRs via alternative splicing. The two spliced isoforms show altered cellular and tissue distributions and behave differently in polysomal recruitment assays in the presence of the drug rapamycin. We propose that repression is therefore the sum of a series of interplaying negative elements within the 5' UTRs, a situation which may reflect the need for tight translational control of ELK-1 in different tissues and under changing physiological conditions.


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