Studying the control of gene expression in Leishmania: post-translational modification, non coding RNAs, cis-elements and gene amplification

Abstract

Leishmania is an ancestral eukaryote and a human parasite of medical relevance. As a model organism it exhibits several odd biological process, mainly in what it concerns to RNA. This proposal's objectives are to decipher molecular f mechanisms to stand different modes of post-transcriptional regulation of gene expression in Leishmania. We aim to study conserved sequences present at the 3'UTRs of parasite's mRNAs. Another target of our study are the non coding RNAs (ncRNAs) which control gene expression throughout Leishmania life cycle and may be critical for the parasite adaptation to each host. We will investigate post-translational processes and gene amplification focused on their role on the control of gene expression in Leishmania. Our objectives are: (1) To study mechanisms of action of conserved 3'UTR sequences to control RNA "turnover" and/or translation in both stages of development in Leishmania, and to understand whether they are involved in the control of "transcriptional regulons' in the parasite; (2) To study ncRNAs function in Leishmania using highthrouput sequencing data (RNA-seq) and to select from the non-coding RNA sequence data generated a few ncRNAs differentially expressed in promastigotes/amastigotes to investigate their potential role in the regulation of gene expression and pathogenesis; (3) to study the biogenesis of ODD3, a putative non coding RNA, its mechanism of action and mRNA targets; (4) to investigate some epigenetic factors involved in the control of gene expression in leishmania such as protein methylation an degradation pathways and (5) characterization of gene amplification control played by the enzymes LmHus1 and LmRad9, which are part of the machinery involved in signaling of DNA damage. (AU)