51. Schistosoma mansoni coactivator associated arginine methyltransferase 1 (SmCARM1) effect on parasite reproduction.
- Author
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Coelho FS, Gava SG, Andrade LF, Geraldo JA, Tavares NC, Lunkes FMN, Neves RH, Machado-Silva JR, Pierce RJ, Oliveira G, and Mourão MM
- Abstract
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 Sm carm 1 expression which is enriched in clusters of ambiguous cells and Sm prmt 1 in NDF+ neurons and stem/germinal cells from schistosomula. Sm prmt 1 is also enriched in S1 and late female germ cells from adult worms. After dsRNA exposure in vitro , we observed a Sm carm 1 knockdown in schistosomula and adult worms, 83 and 69%, respectively. Sm carm 1-knockdown resulted in reduced oviposition and no significant changes in the schistosomula or adult worm phenotypes. In vivo analysis after murine infection with Sm carm 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 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 Sm carm 1 knockdown are a consequence of the SmCARM1-mediated methylation of histone tails involved in DNA packaging or other non-histone proteins., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Coelho, Gava, Andrade, Geraldo, Tavares, Lunkes, Neves, Machado-Silva, Pierce, Oliveira and Mourão.)
- Published
- 2023
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