Analysis of modulation of expression of a putative Leishmania major aminoacyl tRNA-protein transferase under different stress conditions

• Grant number: 17/01713-1
• Support type: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): March 01, 2017
• Effective date (End): December 31, 2017
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal researcher: Angela Kaysel Cruz
• Grantee: Angela Poletto
• Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 13/50219-9 - Studying the control of gene expression in Leishmania: post-translational modification, non coding RNAs, cis-elements and gene amplification, AP.TEM

Abstract

The parasite Leishmania is exposed to different hostile environments. Therefore the adaptation to stress stimuli is part of its life cycle. Most of the adaptive mechanisms of this parasite consists of modulating gene expression profile. This regulation is mostly performed by post-transcriptional and post-translational processes. Among post-translational regulatory processes there is a pathway of directed proteolysis known as the "N-end rule" pathway, which promotes the addition of an amino acid to the N-terminus of several proteins, marking them to be polyubiquitinated and degraded by the proteasome. Although considered a universal signaling process, this pathway is not yet described in Leishmania. In studies conducted in our laboratory the protein encoded by the LmjF.21.0725 gene was characterized as a probable aminoacyl-tRNA-protein transferase, the enzyme that catalyzes the transfer of the amino acid to the N-terminal residue. Preliminary results suggest that it is modulated in Leishmania major promastigotes under oxidative stress. In other organisms, both prokaryotes and eukaryotes, this pathway is activated by several stress stimuli. To understand the role of this protein in Leishmania major, this project aims to investigate the modulation of transcript levels and the aminoacyl-tRNA protein transferase levels in different stress conditions; Oxidative (H2O2) and thermal stress, endoplasmic reticulum stress (Tunicamycin) and by inhibition of protein synthesis (G418). (AU)