Schistosoma mansoni coactivator associated arginine methyltransferase 1 (SmCARM1) effect on parasite reproduction

Detalhes bibliográficos
Autor(a) principal: Coelho, Fernanda Sales
Data de Publicação: 2023
Outros Autores: Gava, Sandra Grossi, Andrade, Luiza Freire, Geraldo, Juliana Assis, Tavares, Naiara Clemente, Lunkes, Felipe Miguel Nery, Neves, Renata Heisler, Machado-Silva, José Roberto, Pierce, Raymond J, Oliveira, Guilherme Corrêa de, Mourão, Marina Moraes
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/57894
Resumo: Fundação Oswaldo Cruz. Instituto René Rachou. Grupo de Pesquisa em Helmintologia e Malacologia Médica. Belo Horizonte, MG, Brazil/Department of Clinical Research, London School of Hygiene and Tropical Medicine, London, United Kingdom.
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spelling Coelho, Fernanda SalesGava, Sandra GrossiAndrade, Luiza FreireGeraldo, Juliana AssisTavares, Naiara ClementeLunkes, Felipe Miguel NeryNeves, Renata HeislerMachado-Silva, José RobertoPierce, Raymond JOliveira, Guilherme Corrêa deMourão, Marina Moraes2023-04-19T18:09:58Z2023-04-19T18:09:58Z2023COELHO, Fernanda Sales et al. Schistosoma mansoni coactivator associated arginine methyltransferase 1 (SmCARM1) effect on parasite reproduction. Frontiers in microbiology, v. 14, 1079855-1079855, 2023. doi: 10.3389/fmicb.2023.1079855.1664-302Xhttps://www.arca.fiocruz.br/handle/icict/57894engFrontiers Research FoundationSchistosoma mansoni coactivator associated arginine methyltransferase 1 (SmCARM1) effect on parasite reproductioninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto René Rachou. Grupo de Pesquisa em Helmintologia e Malacologia Médica. Belo Horizonte, MG, Brazil/Department of Clinical Research, London School of Hygiene and Tropical Medicine, London, United Kingdom.Fundação Oswaldo Cruz. Instituto René Rachou. Grupo de Pesquisa em Helmintologia e Malacologia Médica. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Instituto René Rachou. Grupo de Pesquisa em Helmintologia e Malacologia Médica. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Instituto René Rachou. Grupo de Pesquisa em Helmintologia e Malacologia Médica. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Instituto René Rachou. Grupo de Pesquisa em Helmintologia e Malacologia Médica. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Instituto René Rachou. Grupo de Pesquisa em Helmintologia e Malacologia Médica. Belo Horizonte, MG, Brazil.Universidade do Estado do Rio de Janeiro. Faculdade de Ciências Médicas. Departamento de Microbiologia, Imunologia e Parasitologia. Laboratório de Helmintologia Romero Lascasas Porto. Rio de Janeiro, RJ, Brazil.Universidade do Estado do Rio de Janeiro. Faculdade de Ciências Médicas. Departamento de Microbiologia, Imunologia e Parasitologia. Laboratório de Helmintologia Romero Lascasas Porto. Rio de Janeiro, RJ, Brazil.Université de Lille. CNRS. Inserm. CHU Lille. Institut Pasteur de Lille. U1019-UMR 9017-CIIL-Centre d'Infection et d'Immunité de Lille. Lille, France.Fundação Oswaldo Cruz. Instituto René Rachou. Grupo de Pesquisa em Helmintologia e Malacologia Médica. Belo Horizonte, MG, Brazil/Instituto Tecnológico Vale. Belém, PA, Brazil.Fundação Oswaldo Cruz. Instituto René Rachou. Grupo de Pesquisa em Helmintologia e Malacologia Médica. Belo Horizonte, MG, Brazil.Introduction: The human blood fluke parasite Schistosoma mansoni relies on diverse mechanisms to adapt to its diverse environments and hosts. Epigenetic mechanisms play a central role in gene expression regulation, culminating in such adaptations. Protein arginine methyltransferases (PRMTs) promote posttranslational modifications, modulating the function of histones and non-histone targets. The coactivator-associated arginine methyltransferase 1 (CARM1/PRMT4) is one of the S. mansoni proteins with the PRMT core domain. Methods: We carried out in silico analyses to verify the expression of SmPRMTs in public datasets from different infection stages, single-sex versus mixed-worms, and cell types. The SmCARM1 function was evaluated by RNA interference. Gene expression levels were assessed, and phenotypic alterations were analyzed in vitro, in vivo, and ex vivo. Results: The scRNAseq data showed that SmPRMTs expression is not enriched in any cell cluster in adult worms or schistosomula, except for Smcarm1 expression which is enriched in clusters of ambiguous cells and Smprmt1 in NDF+ neurons and stem/germinal cells from schistosomula. Smprmt1 is also enriched in S1 and late female germ cells from adult worms. After dsRNA exposure in vitro, we observed a Smcarm1 knockdown in schistosomula and adult worms, 83 and 69%, respectively. Smcarm1-knockdown resulted in reduced oviposition and no significant changes in the schistosomula or adult worm phenotypes. In vivo analysis after murine infection with Smcarm1 knocked-down schistosomula, showed no significant change in the number of worms recovered from mice, however, a significant reduction in the number of eggs recovered was detected. The ex vivo worms presented a significant decrease in the ovary area with a lower degree of cell differentiation, vitelline glands cell disorganization, and a decrease in the testicular lobe area. The worm tegument presented a lower number of tubercles, and the ventral sucker of the parasites presented a damaged tegument and points of detachment from the parasite body. Discussion: This work brings the first functional characterization of SmCARM1 shedding light on its roles in S. mansoni biology and its potential as a drug target. Additional studies are necessary to investigate whether the reported effects of Smcarm1 knockdown are a consequence of the SmCARM1-mediated methylation of histone tails involved in DNA packaging or other non-histone proteins.Schistosoma mansoniSmCARM1coactivator associated arginine methyltransferase 1epigenetics; reproduction.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/57894/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALSchistosoma mansoni coactivator associated.pdfSchistosoma mansoni coactivator associated.pdfapplication/pdf5051252https://www.arca.fiocruz.br/bitstream/icict/57894/2/Schistosoma%20mansoni%20coactivator%20associated.pdf8bcc501b6175344fc35df8dd6cd655dcMD52icict/578942023-04-19 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dc.title.en_US.fl_str_mv Schistosoma mansoni coactivator associated arginine methyltransferase 1 (SmCARM1) effect on parasite reproduction
title Schistosoma mansoni coactivator associated arginine methyltransferase 1 (SmCARM1) effect on parasite reproduction
spellingShingle Schistosoma mansoni coactivator associated arginine methyltransferase 1 (SmCARM1) effect on parasite reproduction
Coelho, Fernanda Sales
Schistosoma mansoni
SmCARM1
coactivator associated arginine methyltransferase 1
epigenetics; reproduction.
title_short Schistosoma mansoni coactivator associated arginine methyltransferase 1 (SmCARM1) effect on parasite reproduction
title_full Schistosoma mansoni coactivator associated arginine methyltransferase 1 (SmCARM1) effect on parasite reproduction
title_fullStr Schistosoma mansoni coactivator associated arginine methyltransferase 1 (SmCARM1) effect on parasite reproduction
title_full_unstemmed Schistosoma mansoni coactivator associated arginine methyltransferase 1 (SmCARM1) effect on parasite reproduction
title_sort Schistosoma mansoni coactivator associated arginine methyltransferase 1 (SmCARM1) effect on parasite reproduction
author Coelho, Fernanda Sales
author_facet Coelho, Fernanda Sales
Gava, Sandra Grossi
Andrade, Luiza Freire
Geraldo, Juliana Assis
Tavares, Naiara Clemente
Lunkes, Felipe Miguel Nery
Neves, Renata Heisler
Machado-Silva, José Roberto
Pierce, Raymond J
Oliveira, Guilherme Corrêa de
Mourão, Marina Moraes
author_role author
author2 Gava, Sandra Grossi
Andrade, Luiza Freire
Geraldo, Juliana Assis
Tavares, Naiara Clemente
Lunkes, Felipe Miguel Nery
Neves, Renata Heisler
Machado-Silva, José Roberto
Pierce, Raymond J
Oliveira, Guilherme Corrêa de
Mourão, Marina Moraes
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Coelho, Fernanda Sales
Gava, Sandra Grossi
Andrade, Luiza Freire
Geraldo, Juliana Assis
Tavares, Naiara Clemente
Lunkes, Felipe Miguel Nery
Neves, Renata Heisler
Machado-Silva, José Roberto
Pierce, Raymond J
Oliveira, Guilherme Corrêa de
Mourão, Marina Moraes
dc.subject.en.en_US.fl_str_mv Schistosoma mansoni
SmCARM1
coactivator associated arginine methyltransferase 1
epigenetics; reproduction.
topic Schistosoma mansoni
SmCARM1
coactivator associated arginine methyltransferase 1
epigenetics; reproduction.
description Fundação Oswaldo Cruz. Instituto René Rachou. Grupo de Pesquisa em Helmintologia e Malacologia Médica. Belo Horizonte, MG, Brazil/Department of Clinical Research, London School of Hygiene and Tropical Medicine, London, United Kingdom.
publishDate 2023
dc.date.accessioned.fl_str_mv 2023-04-19T18:09:58Z
dc.date.available.fl_str_mv 2023-04-19T18:09:58Z
dc.date.issued.fl_str_mv 2023
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv COELHO, Fernanda Sales et al. Schistosoma mansoni coactivator associated arginine methyltransferase 1 (SmCARM1) effect on parasite reproduction. Frontiers in microbiology, v. 14, 1079855-1079855, 2023. doi: 10.3389/fmicb.2023.1079855.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/57894
dc.identifier.issn.en_US.fl_str_mv 1664-302X
identifier_str_mv COELHO, Fernanda Sales et al. Schistosoma mansoni coactivator associated arginine methyltransferase 1 (SmCARM1) effect on parasite reproduction. Frontiers in microbiology, v. 14, 1079855-1079855, 2023. doi: 10.3389/fmicb.2023.1079855.
1664-302X
url https://www.arca.fiocruz.br/handle/icict/57894
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Frontiers Research Foundation
publisher.none.fl_str_mv Frontiers Research Foundation
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
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collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/57894/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/57894/2/Schistosoma%20mansoni%20coactivator%20associated.pdf
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