The search for alternative mechanisms driving translation in Leishmania

Translation of most cellular mRNAs in eukaryotes proceeds through a cap-dependent pathway, whereby the cap-binding complex, eIF4F, anchors the pre-initiation complex at the 5’ end of mRNAs and regulates translation initiation. The large repertoire of cap-binding complexes contributes to Leishmania’s survival since each has a role in assisting the parasites in resisting the different and specific stress conditions that they experience during the life cycle. Here we describe a non-canonical pathway that is dependent on the LeishIF3 complex. The eIF3 in mammalian cells was shown to promote transcript-specific translation in a cap-independent manner, also free of known IRES elements. Leishmania cells also possess a cap-binding activity free of the LeishIF4F complex. In our studies towards understanding how the translation machinery in Leishmania is adapted to function under different environments, we aim to identify novel translation factors and interactions which are unique to the parasite cells, and these could serve in the future as novel targets for drug leads.