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

Author(s)

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]}

Affiliation

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

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

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 10, n. 1 DEC 9 2020.
• Web of Science Citations: 4

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. (AU)

• FAPESP's process: 18/19591-2 - Long non-coding RNAs annotation and identification of potential therapeutic targets in Schistosoma mansoni
• Grantee: Lucas Ferreira Maciel
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 18/23693-5 - Mechanisms of action of long non-coding RNAs involved with gene activation programs in eukaryotes
• Grantee: Sergio Verjovski Almeida
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 16/10046-6 - Effect of GSK343, an inhibitor of the histone methyltransferase EZH2, on the parasite Schistosoma mansoni
• Grantee: Adriana Silva Andrade Pereira
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 18/24015-0 - Functional characterization of long non-protein coding RNAs in Schistosoma mansoni
• Grantee: Gilbert de Oliveira Silveira
• Support Opportunities: Scholarships in Brazil - Doctorate