Protein methyltransferase 7 deficiency in Leishmania major increases neutrophil associated pathology in murine model.
Leishmania major is the main causative agent of cutaneous leishmaniasis in the Old World. In Leishmania parasites, the lack of transcriptional control is mostly compensated by post-transcriptional mechanisms. Methylation of arginine is a conserved post-translational modification executed by Protein...
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ftdoajarticles:oai:doaj.org/article:fc6c456a480446dd8f8cc9b8f8b6c3d8 2023-05-15T15:10:12+02:00 Protein methyltransferase 7 deficiency in Leishmania major increases neutrophil associated pathology in murine model. Juliana Alcoforado Diniz Mariana M Chaves Slavica Vaselek Rubens D Miserani Magalhães Rafael Ricci-Azevedo Renan V H de Carvalho Lucas B Lorenzon Tiago R Ferreira Dario Zamboni Pegine B Walrad Petr Volf David L Sacks Angela K Cruz 2021-03-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0009230 https://doaj.org/article/fc6c456a480446dd8f8cc9b8f8b6c3d8 EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0009230 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0009230 https://doaj.org/article/fc6c456a480446dd8f8cc9b8f8b6c3d8 PLoS Neglected Tropical Diseases, Vol 15, Iss 3, p e0009230 (2021) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2021 ftdoajarticles https://doi.org/10.1371/journal.pntd.0009230 2022-12-31T05:04:46Z Leishmania major is the main causative agent of cutaneous leishmaniasis in the Old World. In Leishmania parasites, the lack of transcriptional control is mostly compensated by post-transcriptional mechanisms. Methylation of arginine is a conserved post-translational modification executed by Protein Arginine Methyltransferase (PRMTs). The genome from L. major encodes five PRMT homologs, including the cytosolic protein associated with several RNA-binding proteins, LmjPRMT7. It has been previously reported that LmjPRMT7 could impact parasite infectivity. In addition, a more recent work has clearly shown the importance of LmjPRMT7 in RNA-binding capacity and protein stability of methylation targets, demonstrating the role of this enzyme as an important epigenetic regulator of mRNA metabolism. In this study, we unveil the impact of PRMT7-mediated methylation on parasite development and virulence. Our data reveals that higher levels of LmjPRMT7 can impair parasite pathogenicity, and that deletion of this enzyme rescues the pathogenic phenotype of an attenuated strain of L. major. Interestingly, lesion formation caused by LmjPRMT7 knockout parasites is associated with an exacerbated inflammatory reaction in the tissue correlated with an excessive neutrophil recruitment. Moreover, the absence of LmjPRMT7 also impairs parasite development within the sand fly vector Phlebotomus duboscqi. Finally, a transcriptome analysis shed light onto possible genes affected by depletion of this enzyme. Taken together, this study highlights how post-transcriptional regulation can affect different aspects of the parasite biology. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 15 3 e0009230 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Juliana Alcoforado Diniz Mariana M Chaves Slavica Vaselek Rubens D Miserani Magalhães Rafael Ricci-Azevedo Renan V H de Carvalho Lucas B Lorenzon Tiago R Ferreira Dario Zamboni Pegine B Walrad Petr Volf David L Sacks Angela K Cruz Protein methyltransferase 7 deficiency in Leishmania major increases neutrophil associated pathology in murine model. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Leishmania major is the main causative agent of cutaneous leishmaniasis in the Old World. In Leishmania parasites, the lack of transcriptional control is mostly compensated by post-transcriptional mechanisms. Methylation of arginine is a conserved post-translational modification executed by Protein Arginine Methyltransferase (PRMTs). The genome from L. major encodes five PRMT homologs, including the cytosolic protein associated with several RNA-binding proteins, LmjPRMT7. It has been previously reported that LmjPRMT7 could impact parasite infectivity. In addition, a more recent work has clearly shown the importance of LmjPRMT7 in RNA-binding capacity and protein stability of methylation targets, demonstrating the role of this enzyme as an important epigenetic regulator of mRNA metabolism. In this study, we unveil the impact of PRMT7-mediated methylation on parasite development and virulence. Our data reveals that higher levels of LmjPRMT7 can impair parasite pathogenicity, and that deletion of this enzyme rescues the pathogenic phenotype of an attenuated strain of L. major. Interestingly, lesion formation caused by LmjPRMT7 knockout parasites is associated with an exacerbated inflammatory reaction in the tissue correlated with an excessive neutrophil recruitment. Moreover, the absence of LmjPRMT7 also impairs parasite development within the sand fly vector Phlebotomus duboscqi. Finally, a transcriptome analysis shed light onto possible genes affected by depletion of this enzyme. Taken together, this study highlights how post-transcriptional regulation can affect different aspects of the parasite biology. |
format |
Article in Journal/Newspaper |
author |
Juliana Alcoforado Diniz Mariana M Chaves Slavica Vaselek Rubens D Miserani Magalhães Rafael Ricci-Azevedo Renan V H de Carvalho Lucas B Lorenzon Tiago R Ferreira Dario Zamboni Pegine B Walrad Petr Volf David L Sacks Angela K Cruz |
author_facet |
Juliana Alcoforado Diniz Mariana M Chaves Slavica Vaselek Rubens D Miserani Magalhães Rafael Ricci-Azevedo Renan V H de Carvalho Lucas B Lorenzon Tiago R Ferreira Dario Zamboni Pegine B Walrad Petr Volf David L Sacks Angela K Cruz |
author_sort |
Juliana Alcoforado Diniz |
title |
Protein methyltransferase 7 deficiency in Leishmania major increases neutrophil associated pathology in murine model. |
title_short |
Protein methyltransferase 7 deficiency in Leishmania major increases neutrophil associated pathology in murine model. |
title_full |
Protein methyltransferase 7 deficiency in Leishmania major increases neutrophil associated pathology in murine model. |
title_fullStr |
Protein methyltransferase 7 deficiency in Leishmania major increases neutrophil associated pathology in murine model. |
title_full_unstemmed |
Protein methyltransferase 7 deficiency in Leishmania major increases neutrophil associated pathology in murine model. |
title_sort |
protein methyltransferase 7 deficiency in leishmania major increases neutrophil associated pathology in murine model. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2021 |
url |
https://doi.org/10.1371/journal.pntd.0009230 https://doaj.org/article/fc6c456a480446dd8f8cc9b8f8b6c3d8 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 15, Iss 3, p e0009230 (2021) |
op_relation |
https://doi.org/10.1371/journal.pntd.0009230 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0009230 https://doaj.org/article/fc6c456a480446dd8f8cc9b8f8b6c3d8 |
op_doi |
https://doi.org/10.1371/journal.pntd.0009230 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
15 |
container_issue |
3 |
container_start_page |
e0009230 |
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1766341247933349888 |