Investigation of the function of the arginine methyltransferase LmjPRMT7 on the control of gene expression in Leishmania major

• Grant number: 10/01129-9
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: June 01, 2010
• End date: November 30, 2014
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Angela Kaysel Cruz
• Grantee: Tiago Rodrigues Ferreira
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 13/22222-5 - Analysis of LmjPRMT7 function during Leishmania major development, BE.EP.DR

Abstract

Protozoan parasites of the Leishmania genus constitute a subject of great interest and extensive study in Molecular Biology. However, the biology of such microrganism is not yet well understood. Given the mainly post-transcriptional regulation of gene expression in Leishmania spp. it is possible that different groups of RNA binding proteins play major functions in such control. Recently, studies on mammal and yeast showed important roles of Arginine N-methyltransferases (PRMTs) in this context, and that a large number of RNA associated proteins are substrates for these enzymes. Previous investigations and established concepts on PRMTs and their role in RNA metabolism suggest that a study of PRMTs in Leishmania would be very promising because the post-translational modification performed by PRMTs may occur on key proteins involved in RNA stability and processing control. Therefore we propose the investigation of LmjPRMT7 protein function in L. major, annotated as the ortholog of the Trypanosoma brucei TbPRMT7. To analyze LmjPRMT7 putative functions and related processes we will produce knockout and overexpressor transfectants. A study of global gene expression profile will be carried out on transfectants by transcriptomic and proteomic analyses. Biochemical assays will be used to confirm the methyltransferase activity of the analyzed protein. A series of biochemical experiments and a functional proteomic approach will be conducted to demonstrate its direct interaction with other proteins. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FERREIRA, TIAGO R.; ALVES-FERREIRA, ELIZA V. C.; DEFINA, TANIA P. A.; WALRAD, PEGINE; PAPADOPOULOU, BARBARA; CRUZ, ANGELA K.. Altered expression of an RBP-associated arginine methyltransferase 7 in Leishmania major affects parasite infection. Molecular Microbiology, v. 94, n. 5, p. 1085-1102, DEC 2014. (11/02040-4, 10/01129-9, 10/20597-3, 06/50323-7)

CAMPAGNARO, GUSTAVO DANIEL; LORENZON, LUCAS BIGOLIN; RODRIGUES, MATEUS AUGUSTO; DEFINA, TANIA PAULA AQUINO; PINZAN, CAMILA FIGUEIREDO; FERREIRA, TIAGO RODRIGUES; CRUZ, ANGELA KAYSEL. Overexpression of Leishmania major protein arginine methyltransferase 6 reduces parasite infectivity in vivo. Acta Tropica, v. 244, p. 7-pg., 2023-06-01. (15/13618-8, 14/00220-3, 18/14398-0, 13/13237-9, 20/02372-6, 10/01129-9)