All cells adapt to changes in their environment by regulating the expression of their genes. Our research group studies the functioning of gene expression in eukaryotes and its adaptation to external signals. We aim to understand how changes in gene expression occur by studying its different stages, from transcriptional to post-transcriptional regulation, from DNA information to its use for the synthesis of functional proteins. To do this, we study the synthesis of messenger RNAs (mRNAs) during transcription, we study the binding of proteins to chromatin to regulate this process, we measure the stability of mRNAs and the synthesis of proteins by translation of mRNAs. We are interested in the integration of all these processes and the study of coordinating proteins that move between the nucleus and the cytoplasm to regulate multiple steps in a coordinated manner.

One of the key factors in the control of gene expression at the level of translation and possibly at other stages is the eIF5A protein. This is a very abundant and essential protein in all eukaryotic cells. It is also a protein that is highly conserved in evolution, both in terms of amino acid sequence and three-dimensional structure. Although it was originally classified as a translation initiation factor (hence its acronym eIF: eukaryotic initiation factor), it was later shown to function primarily as a translation elongation factor. eIF5A is essential in eukaryotic cells, but it is not essential for each round of translation elongation. However, its function is essential to prevent the stalling of elongating ribosomes when they encounter sequences in the mRNA that encode consecutive proline motifs (polyPro motifs) or combinations of prolines, glycines and charged amino acids. These types of sequences function poorly as acceptors and donors for peptide bond formation and also cause negative interactions in the exit tunnel region of the nascent peptide in the ribosome, leading to ribosome stalling. eIF5A, activated by post-transcriptional modification of hypusination, is able to interact with the stalled ribosome through the empty E site and promote peptide bond formation, allowing elongation to continue.

In recent years, eIF5A has been implicated in several pathologies including cancer, especially metastatic cancer, viral infections and diabetes. In addition, eIF5A levels decrease with age, while promoting its activity leads to an increase in lifespan in model organisms and an improvement in the immune and cognitive systems in mice and humans. For all these reasons, it is very important to know the mechanisms of action of eIF5A in cells.

We are interested in understanding the mechanism of translation regulation by eIF5A, which proteins require this factor for their synthesis, and how eIF5A acts directly or through its targets in pathological processes such as fibrosis, cancer or ageing. In addition, we want to identify other cellular functions of eIF5A, its function in the nucleus and also in association with mitochondria. In our group, we mainly use the yeast Saccharomyces cerevisiae as a model organism because it is the best known eukaryote and a model for understanding evolutionarily conserved molecular processes at the cellular level. In addition, we investigate whether the conclusions of our research can be generalised to mammalian cells using mouse or human cell cultures.