title: Signaling transcript profile of the asexual intraerythrocytic development cycle ofPlasmodium falciparuminduced by melatonin and cAMP.
abstract: According to the World Health Organization (WHO),Plasmodium falciparumis the deadliest parasite among all species. This parasite possesses the ability to sense molecules, including melatonin (MEL) and cAMP, and modulate its cell cycle accordingly. MEL synchronizes the development of this malaria parasite by activating several cascades, including the generation of the second messenger cAMP. Therefore, we performed RNA sequencing (RNA-Seq) analysis inP. falciparumerythrocytic stages (ring, trophozoite and schizont) treated with MEL and cAMP. To investigate the expression profile ofP. falciparumgenes regulated by MEL and cAMP, we performed RNA-Seq analysis in threeP. falciparumstrains (control, 3D7; protein kinase 7 knockout, PfPK7-; and PfPK7 complement, PfPK7C). In the 3D7 strain, 38 genes were differentially expressed upon MEL treatment; however, none of the genes in the trophozoite (T) stage PfPK7- knockout parasites were differentially expressed upon MEL treatment for 5 hours compared to untreated controls, suggesting that PfPK7 may be involved in the signaling leading to differential gene expression. Moreover, we found that MEL modified the mRNA expression of genes encoding membrane proteins, zinc ion-binding proteins and nucleic acid-binding proteins, which might influence numerous functions in the parasite. The RNA-Seq data following treatment with cAMP show that this molecule modulates different genes throughout the intraerythrocytic cycle, namely, 75, 101 and 141 genes, respectively, in the ring (R), T and schizont (S) stages. Our results highlightP. falciparum's perception of the external milieu through the signaling molecules MEL and cAMP, which are able to drive to changes in gene expression in the parasite.
authors.affiliation: Departamento de Fisiologia, Instituto de Biociências, Universidade de Sao Paulo, Sao Paulo, Brazil.|Instituto de Ciências Exatas e Naturais (ICEN)- Medicina, Universidade Federal do Mato Grosso - Campus Rondonópolis, Brazil.
authors.forename: Wânia Rezende
authors.initials: WR
authors.lastname: Lima
authors.affiliation: Departamento de Fisiologia, Instituto de Biociências, Universidade de Sao Paulo, Sao Paulo, Brazil.
authors.forename: Giulliana
authors.initials: G
authors.lastname: Tessarin-Almeida
authors.affiliation: Centro de Oncologia Molecular, Hospital Sírio-Libanês, Sao Paulo, Brazil.
authors.forename: Andrei
authors.initials: A
authors.lastname: Rozanski
authors.affiliation: Departamento de Imunologia e Parasitologia, Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Brazil.
authors.forename: Kleber S
authors.initials: KS
authors.lastname: Parreira
authors.affiliation: Departamento de Fisiologia, Instituto de Biociências, Universidade de Sao Paulo, Sao Paulo, Brazil.
authors.forename: Miriam S
authors.initials: MS
authors.lastname: Moraes
authors.affiliation: Centro de Matemática, Computação e Cognição, Universidade Federal do ABC, São Paulo, Brazil.
authors.forename: David C
authors.initials: DC
authors.lastname: Martins
authors.affiliation: Departamento de Ciência da Computação, Instituto de Matemática e Estatística, Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Ronaldo F
authors.initials: RF
authors.lastname: Hashimoto
authors.affiliation: Centro de Oncologia Molecular, Hospital Sírio-Libanês, Sao Paulo, Brazil.
authors.forename: Pedro A F
authors.initials: PAF
authors.lastname: Galante
authors.affiliation: Departamento de Fisiologia, Instituto de Biociências, Universidade de Sao Paulo, Sao Paulo, Brazil.
authors.forename: Célia R S
authors.initials: CRS
authors.lastname: Garcia
keywords: P. falciparum; cAMP; malaria; melatonin; transcripts; ubiquitin proteasome