Ricerc@Sapienza

The importance of translational regulation in the fine-tuning of gene expression is being increasingly recognized. There is an ample literature describing how an excess (or dearth) of certain translation factors, and even of ribosomal proteins, may affect cell physiology and behavior, altering differentiation patterns, dealing with stress signals, or even steering the cells towards tumoral transformation. In most known cases, these events depend on an alteration of the translational landscape, whereby specific subsets of mRNAs are preferentially loaded on (or excluded from) polysomes, leading to the selective increase (or decrease) of certain key proteins involved in controlling crucial cellular processes such as, for instance, the cell cycle. The role of certain translation factors in determining selective translation is well understood. For instance, the eukaryotic cap-binding factor eIF4E is a bone fide oncogene which, when over-expressed, causes an increase in the translation of certain proteins controlling cell proliferation by enhancing polysome loading of the relative mRNAs. However, there are several other factors whose function in translational control is much less understood. The translational factor termed IF6 belongs in this category. This protein is conserved in evolution, being present in both the eukaryotes and the archaea. Many reports indicate that, in eukaryotes, eIF6 is involved in modulating translation in differentiation, stress and cancer. However, the underlying molecular mechanisms are far from being clear. The general aim of the present project is to unravel the role of eIF6 in translational control in eukaryotes, highlighting the role it plays in specialized processes such as translation and ribosome biogenesis.