The translation factor 5A (eIF5A) is conserved and essential for cell viability. This is the only protein known to contain the amino acid residue hypusine, essential for eIF5A function, generated by a post-translational modification. Although it was initially suggested a function for eIF5A in the translation initiation, eIF5A has been demonstrated to have a role in translation elongation. More recent studies have established that eIF5A is necessary for the elongation of consecutive proline-containing sequences (poly-P), which are able to induce a ribosome stalling due to low reactivity of proline to form peptide bonds. Data from our group, using budding yeast, revealed a possible role for eIF5A in the secretory pathway and translocation into the Endoplasmic Reticulum (ER), suggesting an involvement of eIF5A on the translation of specific mRNAs of secreted proteins. In addition, it has been suggested an activation of the ER stress response upon eIF5A depletion in mammalian cells. Our unpublished data using an in vivo proteome profile of the ORFs-GFP collection in a hyp2-3 mutant background demonstrating that yeast eIF5A shows several mitochondrial proteins downregulated in the eIF5A mutant. Interestingly, the slowdown of translation elongation rates by rare codons or other translation stalling motifs can facilitate binding of the Signal Recognition Particle (SRP) to the ribosome, which may interfere with ER targeting. Thus, there are different ways by which eIF5A could interfere with translation of proteins targeted to the mitochondria or the ER and further work are necessary to address the mechanisms underlying this role of eIF5A in the cell. Considering this, the aim of this project is to determine which mRNA stretches are protected by eIF5A-bound ribosomes and to study the impact of eIF5A function in the translation of mRNAs bound to membranes.
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