Discussion

Exposure to changing environmental conditions can induce a global translation arrest, to prevent misfolding of de-novo synthesized proteins, and allow the synthesis of selected proteins. Translation arrest is achieved by inhibition of cap-dependent initiation, whereas the synthesis of specific proteins can via cap-independent mechanisms. Leishmanias must adapt their proteomic profiles to the changing hosts and environments, this is achieved mostly by control of translation. We found that trypanosomatids encode for an unusual large repertoire of paralogs of translation initiation factors, which vary extensively in sequence, structure and function. To date, six paralogs of the cap-binding protein eIF4E have been identified, and a similar number of paralogs for the eIF4G scaffold proteins. Our studies show that discrete cap-binding complexes have evolved to function under specific stress conditions, which include both abiotic stresses along with a temporary nutritional scarcity, experienced during metacyclogenesis. Furthermore, we have identified unique and novel proteins that interact with specific cap-binding proteins, forming a network that modulates their function. These regulators are unique only to trypanosomatids. They appear to assist in the remarkable adaptation of their protein synthesis machinery to the changing conditions and to the formation of unique RNA storage granules, under conditions of temporary translation arrest.