Altered expression of an RBP-associated arginine methyltransferase 7 in Leishmania major affects parasite infection

Author(s)

Ferreira, Tiago R. ^[1] ; Alves-Ferreira, Eliza V. C. ^[1] ; Defina, Tania P. A. ^[1] ; Walrad, Pegine ^[2] ; Papadopoulou, Barbara ^[3] ; Cruz, Angela K. ^[1]

Affiliation

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Cell & Mol Biol, BR-14049 Ribeirao Preto - Brazil

^[2] Univ York, Dept Biol, Ctr Immunol & Infect, York YO10 5DD, N Yorkshire - England

^[3] Univ Laval, Fac Med, CHU Quebec Res Ctr CHUL, Res Ctr Infect Dis, Quebec City, PQ G1K 7P4 - Canada

• Document type: Journal article
• Source: Molecular Microbiology; v. 94, n. 5, p. 1085-1102, DEC 2014.
• Web of Science Citations: 12

Abstract

Protein arginine methylation is a widely conserved post-translational modification performed by arginine methyltransferases (PRMTs). However, its functional role in parasitic protozoa is still under-explored. The Leishmania major genome encodes five PRMT homologs, including PRMT7. Here we show that LmjPRMT7 expression and arginine monomethylation are tightly regulated in a lifecycle stage-dependent manner. LmjPRMT7 levels are higher during the early promastigote logarithmic phase, negligible at stationary and late-stationary phases and rise once more post-differentiation to intracellular amastigotes. Immunofluorescence and co-immunoprecipitation studies demonstrate that LmjPRMT7 is a cytosolic protein associated with several RNA-binding proteins (RBPs) from which Alba20 is monomethylated only in LmjPRMT7-expressing promastigote stages. In addition, Alba20 protein levels are significantly altered in stationary promastigotes of the LmjPRMT7 knockout mutant. Considering RBPs are well-known mammalian PRMT substrates, our data suggest that arginine methylation via LmjPRMT7 may modulate RBP function during Leishmania spp. lifecycle progression. Importantly, genomic deletion of the LmjPRMT7 gene leads to an increase in parasite infectivity both in vitro and in vivo, while lesion progression is significantly reduced in LmjPRMT7-overexpressing parasites. This study is the first to describe a role of Leishmania protein arginine methylation in host-parasite interactions. (AU)

• FAPESP's process: 11/02040-4 - The role of Prostaglandin F2-alpha synthase in the interaction of Leishmania braziliensis with the mammalian host
• Grantee: Eliza Vanessa Carneiro Alves Ferreira
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 10/01129-9 - Investigation of the function of the arginine methyltransferase LmjPRMT7 on the control of gene expression in Leishmania major
• Grantee: Tiago Rodrigues Ferreira
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 10/20597-3 - Host-parasite interaction: models for studying virulence and tropism
• Grantee: Angela Kaysel Cruz
• Support Opportunities: Regular Research Grants
• FAPESP's process: 06/50323-7 - Control of gene expression and genetlc plasticity in Leishmania
• Grantee: Angela Kaysel Cruz
• Support Opportunities: Research Projects - Thematic Grants