The N-End rule in Leishmania major: Functional characterization and regulation of gene expression of the Leucyl, Phenylalanyl-tRNA-Protein transferase

Abstract

Although the investigation of post transcriptional regulatory mechanisms in Leishmania is actively undertaken, there is little documentation available on particular roles of post-translational events such as protein stability and modification to the stress response. In many eukaryotes and prokaryotes "last minute" regulatory mechanisms at post-translational level in response to stress involve N-end rule pathway. The N-end rule pathway is considered to be an universal mechanism for triggering specific sets of protein, but it has not yet been characterized in Leishmania spp. In the laboratory of Prof. Angela K. Cruz recent investigation of a gene with uncommon features, named ODD3, revealed its regulatory role as a non-coding RNA candidate which has as its potential mRNA target a hypothetical protein-coding gene (LmjF21.0725) containing a conserved domain for a Leucyl/Phenylalanyl-t RNA transferase (L/F transferase). The key objective of this project is to provide evidence of the functional "N- end rule pathway" in Leishmania parasite by characterization of an important enzyme of this pathway, Leucyl/Phenylalanyl-tRNA transferase (L/F transferase) which has shown to be regulated by a novel non coding RNA ODD3 in promastigote stage. Further the molecular mechanism involved in the regulation of expression of this gene would be investigated in bigenic life cycle stages of this parasite.