Details

Autor(en) / Beteiligte

• 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
• Mourão, Marina Moraes

Titel

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

Ist Teil von

• Frontiers in microbiology, 2023-02, Vol.14, p.1079855-1079855

Ort / Verlag

Switzerland: Frontiers Media S.A

Erscheinungsjahr

2023

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• The human blood fluke parasite 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 proteins with the PRMT core domain. We carried out 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 , , and . The scRNAseq data showed that SmPRMTs expression is not enriched in any cell cluster in adult worms or schistosomula, except for Sm 1 expression which is enriched in clusters of ambiguous cells and Sm 1 in NDF+ neurons and stem/germinal cells from schistosomula. Sm 1 is also enriched in S1 and late female germ cells from adult worms. After dsRNA exposure , we observed a Sm 1 knockdown in schistosomula and adult worms, 83 and 69%, respectively. Sm 1-knockdown resulted in reduced oviposition and no significant changes in the schistosomula or adult worm phenotypes. analysis after murine infection with Sm 1 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 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. This work brings the first functional characterization of SmCARM1 shedding light on its roles in biology and its potential as a drug target. Additional studies are necessary to investigate whether the reported effects of Sm 1 knockdown are a consequence of the SmCARM1-mediated methylation of histone tails involved in DNA packaging or other non-histone proteins.