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

Autor(es)

Amaral, Murilo S. ^[1] ; Maciel, Lucas F. ^[1] ; Silveira, Gilbert O. ^{[2, 1]} ; Olberg, Giovanna G. O. ^[1] ; Leite, Joao V. P. ^[1] ; Imamura, Lucas K. ^[1] ; Pereira, Adriana S. A. ^{[2, 1]} ; Miyasato, Patricia A. ^[1] ; Nakano, Eliana ^[1] ; Verjovski-Almeida, Sergio ^{[2, 1]}

Afiliação do(s) autor(es)

^[1] Inst Butantan, Lab Parasitol, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Quim, Dept Bioquim, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 10, n. 1 DEC 9 2020.
• Citações Web of Science: 4

Resumo

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. (AU)

• Processo FAPESP: 18/19591-2 - Anotação de RNAs longos não-codificantes e identificação de potenciais alvos terapêuticos em Schistosoma mansoni
• Beneficiário: Lucas Ferreira Maciel
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 18/23693-5 - Mecanismos de ação de RNAs longos não-codificadores envolvidos nos programas de ativação gênica em eucariotos
• Beneficiário: Sergio Verjovski Almeida
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 16/10046-6 - Efeito de GSK343, um inibidor da histona metiltransferase EZH2, sobre o parasita Schistosoma mansoni
• Beneficiário: Adriana Silva Andrade Pereira
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 18/24015-0 - Caracterização funcional de RNAs longos não-codificadores de proteínas em Schistosoma mansoni
• Beneficiário: Gilbert de Oliveira Silveira
• Modalidade de apoio: Bolsas no Brasil - Doutorado