Our aims are focused to understand the principles guiding alternative mechanisms of translation initiation in eukaryotes through the characterization of RNA-binding proteins (RBPs) interacting with mRNAs. Internal ribosome entry sites (IRES) are non-coding RNA regions that substitute the function of the 5’ terminal cap of mRNAs, the anchoring point of the translation machinery. Our studies allowed the identification of proteins modulating IRES activity and the understanding of structural constraints which are essential for IRES activity. We have shown that Gemin5 interacts with viral IRES as well as a selective group of cellular mRNAs. Gemin5 is a multitasking protein that forms part of the survival of motor neuron (SMN) complex, and also performs a translation regulatory role. The N-terminal domain of Gemin5 is involved in the interaction with the ribosome and the snRNAs, whereas the C-terminal region harbors a dimerization module and a non-conventional RNA-binding site (RBS). The dimerization domain consisting of a tetratricopeptide (TPR)-like domain that self-assembles into a canoe-shaped dimer.