Analysis of LeishIF4E2, a unique cap binding protein in Leishmania

Leishmania parasites cycle between sand-fly vectors and mammalian hosts, transforming from extracellular promastigotes to obligatory intracellular non-motile amastigotes that reside in the macrophages of the mammalian hosts. The transition between these two environments exposes the parasites to a broad range of environmental conditions that induces a developmental program of gene expression, where translation regulation plays a key role. Leishmania has six paralogs of the cap binding translation initiation factors eIF4E, denoted LeishIF4E 1-6, and 5 paralogs of eIF4G. Two of the LeishIF4Es do not pair with any of the LeishIF4Gs, one being LeishIF4E2. Pull down experiments of tagged LeishIF4E2 show that it forms a complex with the stem and loop binding protein 2, SLBP2, which in higher eukaryotes binds the 3` UTRs of histone mRNAs. Indeed, changes in histone expression were observed in the hemizygous mutant of LeishIF4E2, in which one of the two alleles were eliminated generating LeishIF4E2(+/-). Other mutants of LeishIF4E2 were also examined in attempt to follow the effects on histone expression, using synchronized cells. We aim to show that LeishIF4E2 could affect translation of specific transcripts of Leishmania.