Actions coordinated by the enzyme Arginine Methyltransferase 5 of Leishmania braziliensis

• Grant number: 20/02372-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: September 01, 2020
• End date: December 31, 2023
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Angela Kaysel Cruz
• Grantee: Gustavo Daniel Campagnaro
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 18/14398-0 - UK:Brazil Joint Centre Partnership in Leishmaniasis (JCPiL), AP.TEM

Abstract

The family Trypanosomatidae comprises a group of protozoan parasites that branched early during the evolution of eukaryotes. Among the trypanosomatids, parasites from the genera Trypanosoma (causative agents of Sleeping Sickness and Chagas Disease) and Leishmania (causative agents of Leishmaniases) are the most recognised. Different from most eukaryotes, trypanosomatids present polycistronic transcription and post-transcriptional control of gene expression, which is mediated by the activity of RNA Binding Proteins (RBPs). The activity of many RBPs is coordinated by the methylation of Arginine residues mediated by Protein Arginine Transferases (PRMTs), which leads to an increase or to a decrease in the affinity of RBPs for their target RNAs and impacts gene expression control. Five PRMTs were identified in the Leishmania spp. genomes, and A. Cruz's laboratory pioneers their study. PRMT7 from L. major has been studied and was identified as a negative regulator of infection, given its gene deletion causes an increase in parasite infectivity. Studies from our laboratory have shown that the PRMT5 from L. braziliensis, despite having an expression profile similar to that observed for PRMT7, acts in an opposite fashion, given its gene deletion leads to a decreased infectivity. LbrPRMT5 was found to form specific interactions with four other proteins whose activity might be the direct responsible for this reduction in infection capacity. Therefore, we herein propose to do the biochemical characterisation of LbrPRMT5 and to study the impact of the methylation of its target proteins during cell infection, assessing their role as RBPs and as modulators of gene expression in L. braziliensis. (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)

CAMPAGNARO, GUSTAVO D.; NAY, EDWARD; PLEVIN, MICHAEL J.; CRUZ, ANGELA K.; WALRAD, PEGINE B.. Arginine Methyltransferases as Regulators of RNA-Binding Protein Activities in Pathogenic Kinetoplastids. FRONTIERS IN MOLECULAR BIOSCIENCES, v. 8, JUN 11 2021. (18/14398-0, 20/02372-6, 15/13618-8)

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)

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)