title: La enhances IRES-mediated translation of laminin B1 during malignant epithelial to mesenchymal transition.
abstract: The majority of transcripts that harbor an internal ribosome entry site (IRES) are involved in cancer development via corresponding proteins. A crucial event in tumor progression referred to as epithelial to mesenchymal transition (EMT) allows carcinoma cells to acquire invasive properties. The translational activation of the extracellular matrix component laminin B1 (LamB1) during EMT has been recently reported suggesting an IRES-mediated mechanism. In this study, the IRES activity of LamB1 was determined by independent bicistronic reporter assays. Strong evidences exclude an impact of cryptic promoter or splice sites on IRES-driven translation of LamB1. Furthermore, no other LamB1 mRNA species arising from alternative transcription start sites or polyadenylation signals were detected that account for its translational control. Mapping of the LamB1 5'-untranslated region (UTR) revealed the minimal LamB1 IRES motif between -293 and -1 upstream of the start codon. Notably, RNA affinity purification showed that the La protein interacts with the LamB1 IRES. This interaction and its regulation during EMT were confirmed by ribonucleoprotein immunoprecipitation. In addition, La was able to positively modulate LamB1 IRES translation. In summary, these data indicate that the LamB1 IRES is activated by binding to La which leads to translational upregulation during hepatocellular EMT.
authors: Department of Medicine I, Division: Institute of Cancer Research, Comprehensive Cancer Center Vienna, Medical University of Vienna, Borschkegasse 8a, 1090 Vienna, Austria.
authors: Michaela
authors: M
authors: Petz
authors: Nicole
authors: N
authors: Them
authors: Heidemarie
authors: H
authors: Huber
authors: Hartmut
authors: H
authors: Beug
authors: Wolfgang
authors: W
authors: Mikulits
mesh_terms: D020121:5' Untranslated Regions; D000818:Animals; D001324:Autoantigens / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D006801:Humans; D007797:Laminin / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D009369:Neoplasms / Q000235:genetics; D059372:Nucleotide Motifs; D014176:Protein Biosynthesis; D012326:RNA Splicing; D012333:RNA, Messenger / Q000378:metabolism; D012261:Ribonucleoproteins / Q000378:metabolism*; D014158:Transcription, Genetic; D000097585:SS-B Antigen
chemical_list: D020121:5' Untranslated Regions; D001324:Autoantigens; D007797:Laminin; D012333:RNA, Messenger; D012261:Ribonucleoproteins; D000097585:SS-B Antigen; C478221:LAMB1 protein, human