Methylation mediated by PRMT7 on the differentiation process of promastigotes into amastigotes and the parasite Leishmania major virulence

• Grant number: 16/14657-0
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: November 01, 2016
• End date: March 31, 2019
• Field of knowledge: Biological Sciences - Genetics - Molecular Genetics and Genetics of Microorganisms
• Agreement: MRC, UKRI ; Newton Fund, with FAPESP as a partner institution in Brazil
• Principal Investigator: Angela Kaysel Cruz
• Grantee: Juliana Alcoforado Diniz
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 15/13618-8 - Regulating the trans-regulators: investigating the PRMT7 molecular pathway as an epigenetic regulator of Leishmania virulence, AP.TEM
• Associated scholarship(s): 18/02761-2 - On the role of protein arginine methyltransferase 7 in Leishmania major infectivity and differentiation, BE.EP.PD

Abstract

The differential expression of the PRMT7 enzyme and the differential protein arginine monomethylation profile during Leishmania major development in culture suggest that the arginine methylation process may have a role in parasite differentiation. When we altered the expression of PRMT7 in L. major by knocking out the endogenous gene or overexpressing ectopic copies of the PRMT7 gene, parasite virulence was significantly affected. Since there is a potential link between parasite differentiation and virulence in Leishmania, PRMT7 function may be an indirect regulator of pathogenesis by modulating protein-protein/RNA interactions. We seek to evaluate the amount of the different promastigote forms in the different PRMT7 transfectants or putative RBP mutants and to investigate if amastigote differentiation could be affected. Parasite infectivity and virulence will be analysed in these transfectants using in vitro and in vivo murine models. (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)

RICCI-AZEVEDO, RAFAEL; COSTA MENDONCA-NATIVIDADE, FLAVIA; CAROLINA SANTANA, ANA; ALCOFORADO DINIZ, JULIANA; CRISTINA ROQUE-BARREIRA, MARIA. Microneme Proteins 1 and 4 From Toxoplasma gondii Induce IL-10 Production by Macrophages Through TLR4 Endocytosis. FRONTIERS IN IMMUNOLOGY, v. 12, APR 12 2021. (16/10446-4, 17/02998-0, 18/21708-5, 16/14657-0, 14/13324-1, 13/04088-0)

DINIZ, JULIANA ALCOFORADO; CHAVES, MARIANA M.; VASELEK, SLAVICA; MISERANI MAGALHAES, RUBENS D.; RICCI-AZEVEDO, RAFAEL; DE CARVALHO, RENAN V. H.; LORENZON, LUCAS B.; FERREIRA, TIAGO R.; ZAMBONI, DARIO; WALRAD, PEGINE B.; et al. Protein methyltransferase 7 deficiency in Leishmania major increases neutrophil associated pathology in murine model. PLoS Neglected Tropical Diseases, v. 15, n. 3, MAR 2021. (19/18607-5, 16/14657-0, 18/02761-2, 17/02998-0, 15/13618-8, 16/00969-0)

LORENZON, LUCAS; QUILLES JR, JOSE C.; CAMPAGNARO, GUSTAVO DANIEL; ORSINE, LISSUR AZEVEDO; ALMEIDA, LETICIA; VERAS, FLAVIO; MISERANI MAGALHAES, RUBENS DANIEL; DINIZ, JULIANA ALCOFORADO; FERREIRA, TIAGO RODRIGUES; CRUZ, ANGELA KAYSEL. Functional Study of Leishmania braziliensis Protein Arginine Methyltransferases (PRMTs) Reveals That PRMT1 and PRMT5 Are Required for Macrophage Infection. ACS INFECTIOUS DISEASES, v. 8, n. 3, p. 17-pg., 2022-03-11. (21/10043-5, 20/00088-9, 16/00969-0, 16/14657-0, 15/13618-8, 18/14398-0, 20/02372-6, 19/18607-5)