Evidence for embryonic haemoglobins from Sparus aurata under normal and hypoxic conditions.

Teleost haemoglobins vary in polymorphisms and primary structure, although display similar functional properties. Key amino acids for Root effect (a reduction in oxygen-carrying capacity and loss of cooperativity with declining pH) are conserved throughout fish evolution. For the first time, we cloned and characterised Sparus aurata L. embryonic globin chains (eα1, eα2, eß). We also studied haemoglobins (eHbI, eHbII) behaviour in normal and low-oxygen conditions. Several amino acids in fry globins are different in chemical type (e.g. polar → non-polar and vice versa), compared to adult globins. His55α1, crucial for Root effect, is substituted by Ala in fry, presumably enhancing oxygen capture, transport and reducing the dependence of Root effect from pH. Phylogenetic trees demonstrate that eα1 globin diversified more recently than eα2; moreover, eα1, eα2 and eß globins evolved earlier than adult α and ß globins. In low-oxygen conditions, fry haemoglobins display the same behaviour of the adult haemoglobins (probably, embryonic and adult-type I Hbs display a higher oxygen affinity than type II Hbs, operating through a rapid cycle of heme-Fe auto-oxidation/reduction). Therefore, based on our results and on the comparison with adult haemoglobins, we hypothesise that embryonic haemoglobins have evolved to better adapt fry to variable habitats. We studied Sparus aurata for its economical relevance in Mediterranean aquaculture. The information we provide can help understand Sparus aurata behaviour in the wild and in rearing conditions. Further studies with functional assays will deepen the knowledge on the molecular mechanisms of fry haemoglobin physiology.

Structure and functions of the translation initiation factor eIF4E and its role in cancer development and treatment.

In eukaryotic cells, protein synthesis is a complex and multi-step process that has several mechanisms to start the translation including cap-dependent and cap-independent initiation. The translation control of eukaryotic gene expression occurs principally at the initiation step. In this context, it is critical that the eukaryotic translation initiation factor eIF4E bind to the 7-methylguanosine (m7G) cap present at the 5'-UTRs of most eukaryotic mRNAs. Combined with other initiation factors, eIF4E mediates the mRNA recruitment on ribosomes to start the translation. Moreover, the eIF4E nuclear bodies are involved in the export of specific mRNAs from the nucleus to the cytoplasm. In this review, we focus on the eIF4E structure and its physiological functions, and describe the role of eIF4E in cancer development and progression and the current therapeutic strategies to target eIF4E.