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Nucleic Acids Research Advance Access published online on July 4, 2008
Nucleic Acids Research, doi:10.1093/nar/gkn391
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© 2008 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

The structure of the 5'-end of the protein-tyrosine phosphatase PTPRJ mRNA reveals a novel mechanism for translation attenuation

Luchezar Karagyozov1, Rinesh Godfrey1, Sylvia-Annette Böhmer1, Astrid Petermann1, Sebastian Hölters1, Arne Östman2 and Frank-D. Böhmer1,*

1Institute of Molecular Cell Biology, Center for Molecular Biomedicine, Friedrich-Schiller-University Jena, Jena, Germany and 2Cancer Center Karolinska, Karolinska Institute, Stockholm, Sweden

*To whom correspondence should be addressed. Tel: +49 3641 9325660; Fax: +49 3641 9325652; Email: i5frbo{at}rz.uni-jena.de

Received March 14, 2008. Revised May 30, 2008. Accepted June 4, 2008.

Analysis of the human protein-tyrosine phosphatase (PTP) PTPRJ mRNA detected three in-frame AUGs at the 5'-end (starting at nt +14, +191 and +356) with no intervening stop codons. This tandem AUG arrangement is conserved between humans and the mouse and is unique among the genes of the classical PTPs. Until now it was assumed that the principal open reading frame (ORF) starts at AUG356. Our experiments showed that: (i) translation of the mRNA synthesized under the PTPRJ promoter starts predominantly at AUG191, leading to the generation of a 55 amino acid sequence preceding the signal peptide; (ii) the longer form is being likewise correctly processed into mature PTPRJ; (iii) the translation of the region between AUG191 and AUG356 inhibits the overall expression, a feature which depends on the sequence of the encoded peptide. Specifically, a sequence of 13 amino acids containing multiple arginine residues (RRTGWRRRRRRRR) confers the inhibition. In the absence of uORF these previously unrecognized characteristics of the 5'-end of the mRNA present a novel mechanism to suppress, and potentially to regulate translation.

Present address: Sebastian Hölters, Research Unit Gynecological Molecular Biology, Medical Faculty, Friedrich-Schiller-Universität Jena, Germany


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