comparative 3utr analysis allows identification of regulatory clusters that drive ephephrin expression in cancer cell lines比较3 utr分析允许识别管理集群驱动ephephrin表达式在癌症细胞系.pdfVIP

Comparative 3’UTR Analysis Allows Identification of Regulatory Clusters that Drive Eph/ephrin Expression in Cancer Cell Lines 1¤b 1¤a 1 ¨ 2 2 Jennifer Winter *, Stefan Roepcke , Sven Krause , Eva-Christina Muller , Albrecht Otto , Martin Vingron1, Susann Schweiger1,3,4 1 Max-Planck Institute for Molecular Genetics, Berlin-Dahlem, Germany, 2 Max-Delbrueck Center of Molecular Medicine, Berlin, Germany, 3 Department of Dermatology, ´ Charite-Hospital, Berlin, Germany, 4 Department of Neuroscience and Pathology, College of Medicine, University of Dundee, Dundee, United Kingdom 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-stabil