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Functional evaluation of the Leishmania major arginine methyltransferase LmjPRMT6.

Grant number: 13/13237-9
Support type:Scholarships in Brazil - Master
Effective date (Start): October 01, 2013
Effective date (End): February 28, 2015
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal Investigator:Angela Kaysel Cruz
Grantee:Lucas Bigolin Lorenzon
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Given their impact on public health worldwide, protozoan parasites of Leishmania genus have been widely studied. In these ancient eukaryotes gene expression regulation occurs mostly at the post-transcriptional level. In this context, it is known that RNA binding proteins (RBPs) are important protagonists. Recent studies show that Arginine Methyltransferases (PRMTs) play key roles on yeast, and most of its targets are RBPs. Given the importance of the RBPs on post-transcriptional gene expression regulation, proteins involved in RBPs post-translational modification (in this case, PRMTs), because they alter their interaction with RNA become interesting objects of study in Leishmania spp. Our proposal includes: (i) develop molecular tools which allow us to study the functions of PRMT6, (ii) investigate the function and subcellular localization of Leishmania major PRMT6, (iii) identify phenotypic changes associated with growth and virulence (in vivo and in vitro) of PRMT6 mutants (overexpressors or knockout), and (iv) discover PRMT6 targets, opening doors for future research and for a better understanding of how PRMT6 can regulate gene expression. Several transfectants will be created and biochemistry essays will be used to evaluate PRMT6 methyltransferase activity. Immunoprecipitation essays will be used to prove the association of PRMT6 with other proteins. The results should allow the identification of PRMT6 targets and mechanisms of gene expression regulation in this parasite.