Long non-coding RNA levels can be modulated by 5-azacytidine in Schistosoma mansoni

Abstract Schistosoma mansoni is a flatworm that causes schistosomiasis, a neglected tropical disease that affects more than 200 million people worldwide. There is only one drug indicated for treatment, praziquantel, which may lead to parasite resistance emergence. The ribonucleoside analogue 5-azacy...

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Autores principales:	Murilo S. Amaral, Lucas F. Maciel, Gilbert O. Silveira, Giovanna G. O. Olberg, João V. P. Leite, Lucas K. Imamura, Adriana S. A. Pereira, Patricia A. Miyasato, Eliana Nakano, Sergio Verjovski-Almeida
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d5c3edb898084192917b2e847a1a6d94
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spelling	oai:doaj.org-article:d5c3edb898084192917b2e847a1a6d942021-12-02T16:18:05ZLong non-coding RNA levels can be modulated by 5-azacytidine in Schistosoma mansoni10.1038/s41598-020-78669-52045-2322https://doaj.org/article/d5c3edb898084192917b2e847a1a6d942020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78669-5https://doaj.org/toc/2045-2322Abstract Schistosoma mansoni is a flatworm that causes schistosomiasis, a neglected tropical disease that affects more than 200 million people worldwide. There is only one drug indicated for treatment, praziquantel, which may lead to parasite resistance emergence. The ribonucleoside analogue 5-azacytidine (5-AzaC) is an epigenetic drug that inhibits S. mansoni oviposition and ovarian development through interference with parasite transcription, translation and stem cell activities. Therefore, studying the downstream pathways affected by 5-AzaC in S. mansoni may contribute to the discovery of new drug targets. Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides with low or no protein coding potential that have been involved in reproduction, stem cell maintenance and drug resistance. We have recently published a catalog of lncRNAs expressed in S. mansoni life-cycle stages, tissues and single cells. However, it remains largely unknown if lncRNAs are responsive to epigenetic drugs in parasites. Here, we show by RNA-Seq re-analyses that hundreds of lncRNAs are differentially expressed after in vitro 5-AzaC treatment of S. mansoni females, including intergenic, antisense and sense lncRNAs. Many of these lncRNAs belong to co-expression network modules related to male metabolism and are also differentially expressed in unpaired compared with paired females and ovaries. Half of these lncRNAs possess histone marks at their genomic loci, indicating regulation by histone modification. Among a selected set of 8 lncRNAs, half of them were validated by RT-qPCR as differentially expressed in females, and some of them also in males. Interestingly, these lncRNAs are also expressed in other life-cycle stages. This study demonstrates that many lncRNAs potentially involved with S. mansoni reproductive biology are modulated by 5-AzaC and sheds light on the relevance of exploring lncRNAs in response to drug treatments in parasites.Murilo S. AmaralLucas F. MacielGilbert O. SilveiraGiovanna G. O. OlbergJoão V. P. LeiteLucas K. ImamuraAdriana S. A. PereiraPatricia A. MiyasatoEliana NakanoSergio Verjovski-AlmeidaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-17 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Murilo S. Amaral Lucas F. Maciel Gilbert O. Silveira Giovanna G. O. Olberg João V. P. Leite Lucas K. Imamura Adriana S. A. Pereira Patricia A. Miyasato Eliana Nakano Sergio Verjovski-Almeida Long non-coding RNA levels can be modulated by 5-azacytidine in Schistosoma mansoni
description	Abstract Schistosoma mansoni is a flatworm that causes schistosomiasis, a neglected tropical disease that affects more than 200 million people worldwide. There is only one drug indicated for treatment, praziquantel, which may lead to parasite resistance emergence. The ribonucleoside analogue 5-azacytidine (5-AzaC) is an epigenetic drug that inhibits S. mansoni oviposition and ovarian development through interference with parasite transcription, translation and stem cell activities. Therefore, studying the downstream pathways affected by 5-AzaC in S. mansoni may contribute to the discovery of new drug targets. Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides with low or no protein coding potential that have been involved in reproduction, stem cell maintenance and drug resistance. We have recently published a catalog of lncRNAs expressed in S. mansoni life-cycle stages, tissues and single cells. However, it remains largely unknown if lncRNAs are responsive to epigenetic drugs in parasites. Here, we show by RNA-Seq re-analyses that hundreds of lncRNAs are differentially expressed after in vitro 5-AzaC treatment of S. mansoni females, including intergenic, antisense and sense lncRNAs. Many of these lncRNAs belong to co-expression network modules related to male metabolism and are also differentially expressed in unpaired compared with paired females and ovaries. Half of these lncRNAs possess histone marks at their genomic loci, indicating regulation by histone modification. Among a selected set of 8 lncRNAs, half of them were validated by RT-qPCR as differentially expressed in females, and some of them also in males. Interestingly, these lncRNAs are also expressed in other life-cycle stages. This study demonstrates that many lncRNAs potentially involved with S. mansoni reproductive biology are modulated by 5-AzaC and sheds light on the relevance of exploring lncRNAs in response to drug treatments in parasites.
format	article
author	Murilo S. Amaral Lucas F. Maciel Gilbert O. Silveira Giovanna G. O. Olberg João V. P. Leite Lucas K. Imamura Adriana S. A. Pereira Patricia A. Miyasato Eliana Nakano Sergio Verjovski-Almeida
author_facet	Murilo S. Amaral Lucas F. Maciel Gilbert O. Silveira Giovanna G. O. Olberg João V. P. Leite Lucas K. Imamura Adriana S. A. Pereira Patricia A. Miyasato Eliana Nakano Sergio Verjovski-Almeida
author_sort	Murilo S. Amaral
title	Long non-coding RNA levels can be modulated by 5-azacytidine in Schistosoma mansoni
title_short	Long non-coding RNA levels can be modulated by 5-azacytidine in Schistosoma mansoni
title_full	Long non-coding RNA levels can be modulated by 5-azacytidine in Schistosoma mansoni
title_fullStr	Long non-coding RNA levels can be modulated by 5-azacytidine in Schistosoma mansoni
title_full_unstemmed	Long non-coding RNA levels can be modulated by 5-azacytidine in Schistosoma mansoni
title_sort	long non-coding rna levels can be modulated by 5-azacytidine in schistosoma mansoni
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/d5c3edb898084192917b2e847a1a6d94
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Long non-coding RNA levels can be modulated by 5-azacytidine in Schistosoma mansoni

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