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  Comparative 3’UTR analysis allows identification of regulatory clusters that drive Eph/ephrin expression in cancer cell lines

Winter, J., Roepcke, S., Krause, S., Müller, E.-C., Otto, A., Vingron, M., et al. (2008). Comparative 3’UTR analysis allows identification of regulatory clusters that drive Eph/ephrin expression in cancer cell lines. PLoS One, 3(7), e2780-e2780. doi:10.1371/journal.pone.0002780.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-7F78-8 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-7F79-6
Genre: Journal Article
Alternative Title : PloS ONE

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 Creators:
Winter, Jennifer1, Author              
Roepcke, Stefan2, Author
Krause, Sven2, Author
Müller, Eva-Christina, Author
Otto, Albrecht, Author
Vingron, Martin3, Author              
Schweiger, Susann1, Author              
Affiliations:
1Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433549              
2Max Planck Society, ou_persistent13              
3Gene regulation (Martin Vingron), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479639              

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 Abstract: Eph receptors are the largest family of receptor tyrosine kinases. Together with their ligands, the ephrins, they fulfill multiple biological functions. Aberrant expression of Ephs/ephrins leading to increased Eph receptor to ephrin ligand ratios is a critical factor in tumorigenesis, indicating that tight regulation of Eph and ephrin expression is essential for normal cell behavior. The 3'-untranslated regions (3'UTRs) of transcripts play an important yet widely underappreciated role in the control of protein expression. Based on the assumption that paralogues of large gene families might exhibit a conserved organization of regulatory elements in their 3'UTRs we applied a novel bioinformatics/molecular biology approach to the 3'UTR sequences of Eph/ephrin transcripts. We identified clusters of motifs consisting of cytoplasmic polyadenylation elements (CPEs), AU-rich elements (AREs) and HuR binding sites. These clusters bind multiple RNA-stabilizing and destabilizing factors, including HuR. Surprisingly, despite its widely accepted role as an mRNA-stabilizing protein, we further show that binding of HuR to these clusters actually destabilizes Eph/ephrin transcripts in tumor cell lines. Consequently, knockdown of HuR greatly modulates expression of multiple Ephs/ephrins at both the mRNA and protein levels. Together our studies suggest that overexpression of HuR as found in many progressive tumors could be causative for disarranged Eph receptor to ephrin ligand ratios leading to a higher degree of tissue invasiveness.

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Language(s): eng - English
 Dates: 2008-07-23
 Publication Status: Published in print
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Title: PLoS One
  Alternative Title : PloS ONE
Source Genre: Journal
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Pages: - Volume / Issue: 3 (7) Sequence Number: - Start / End Page: e2780 - e2780 Identifier: -