Cap-independent and internal ribosome entry site (IRES)-mediated translational control upon EMT and liver carcinoma progression

The majority of cellular mRNAs harboring an internal ribosome entry site (IRES) in the 5’-untranslated region (UTR) are involved in cancer development via corresponding proteins. We identified and characterized a novel IRES motif in the transcript of the extracellular matrix component Laminin B1 (LamB1) during EMT. The IRES activity of LamB1 was determined by independent bicistronic reporter assays. Mapping of the LamB1 5’-UTR revealed the minimal LamB1 IRES motif between -293 to -1 upstream of the start codon. RNA affinity purification and RNP immunoprecipitation showed that the La protein increasingly interacts with the minimal IRES element upon EMT. Interestingly, TGF-beta regulates the translocation of La to the cytoplasm upon EMT where it positively modulates LamB1 IRES translation (Figure 2). These data indicate that the LamB1 IRES is activated by the interaction with La which leads to translational upregulation during hepatocellular EMT. Further studies will examine the relevance and complexity of cap-independent and IRES-driven translational control in HCC progression.

Figure 2. Translational control of LamB1 IRES during EMT. TGF-beta signaling shuttles La protein from cell nuclei to the cytoplasm. La binds the LamB1 IRES and activates the translation of LamB1 upon EMT.