Long Non-Coding RNA Levels Are Modulated in Schistosoma mansoni following In Vivo Praziquantel Exposure

Author:

Jardim Poli Pedro1,Fischer-Carvalho Agatha1,Tahira Ana Carolina1ORCID,Chan John D.2,Verjovski-Almeida Sergio13ORCID,Sena Amaral Murilo1ORCID

Affiliation:

1. Laboratório de Ciclo Celular, Instituto Butantan, São Paulo 05503-900, SP, Brazil

2. Global Health Institute, University of Wisconsin-Madison, Madison, WI 53792, USA

3. Instituto de Química, Universidade de São Paulo, São Paulo 05508-900, SP, Brazil

Abstract

Schistosomiasis is a disease caused by trematodes of the genus Schistosoma that affects over 200 million people worldwide. For decades, praziquantel (PZQ) has been the only available drug to treat the disease. Despite recent discoveries that identified a transient receptor ion channel as the target of PZQ, schistosome response to this drug remains incompletely understood, since effectiveness relies on other factors that may trigger a complex regulation of parasite gene expression. Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides with low or no protein-coding potential that play important roles in S. mansoni homeostasis, reproduction, and fertility. Here, we show that in vivo PZQ treatment modulates lncRNA levels in S. mansoni. We re-analyzed public RNA-Seq data from mature and immature S. mansoni worms treated in vivo with PZQ and detected hundreds of lncRNAs differentially expressed following drug exposure, many of which are shared among mature and immature worms. Through RT-qPCR, seven out of ten selected lncRNAs were validated as differentially expressed; interestingly, we show that these lncRNAs are not adult worm stage-specific and are co-expressed with PZQ-modulated protein-coding genes. By demonstrating that parasite lncRNA expression levels alter in response to PZQ, this study unravels an important step toward elucidating the complex mechanisms of S. mansoni response to PZQ.

Funder

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Thematic

Conselho Nacional de Desenvolvimento Científico e Tecnológico

CNPq

Publisher

MDPI AG

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3. Zacharia, A., Mushi, V., and Makene, T. (2020). A systematic review and meta-analysis on the rate of human schistosomiasis reinfection. PLoS ONE, 15.

4. WHO (2024, January 09). Global Health Estimates 2020: Disease Burden by Cause, Age, Sex, by Country and by Region, 2000–2019. Geneva, World Health Organization. Available online: https://www.who.int/data/gho/data/themes/mortality-and-global-health-estimates/global-health-estimates-leading-causes-of-dalys.

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