title: Genome-wide identification of microRNA targets in the neglected disease pathogens of the genus Echinococcus.
abstract: MicroRNAs (miRNAs), a class of small non-coding RNAs, are key regulators of gene expression at post-transcriptional level and play essential roles in biological processes such as development. MiRNAs silence target mRNAs by binding to complementary sequences in the 3'untranslated regions (3'UTRs). The parasitic helminths of the genus Echinococcus are the causative agents of echinococcosis, a zoonotic neglected disease. In previous work, we performed a comprehensive identification and characterization of Echinococcus miRNAs. However, current knowledge about their targets is limited. Since target prediction algorithms rely on complementarity between 3'UTRs and miRNA sequences, a major limitation is the lack of accurate sequence information of 3'UTR for most species including parasitic helminths. We performed RNA-seq and developed a pipeline that integrates the transcriptomic data with available genomic data of this parasite in order to identify 3'UTRs of Echinococcus canadensis. The high confidence set of 3'UTRs obtained allowed the prediction of miRNA targets in Echinococcus through a bioinformatic approach. We performed for the first time a comparative analysis of miRNA targets in Echinococcus and Taenia. We found that many evolutionarily conserved target sites in Echinococcus and Taenia may be functional and under selective pressure. Signaling pathways such as MAPK and Wnt were among the most represented pathways indicating miRNA roles in parasite growth and development. Genome-wide identification and characterization of miRNA target genes in Echinococcus provide valuable information to guide experimental studies in order to understand miRNA functions in the parasites biology. miRNAs involved in essential functions, especially those being absent in the host or showing sequence divergence with respect to host orthologs, might be considered as novel therapeutic targets for echinococcosis control.
authors.affiliation: Instituto de Investigaciones en Microbiología y Parasitología Médicas (IMPaM), Facultad de Medicina, Universidad de Buenos Aires (UBA)-Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Buenos Aires, Argentina.
authors.forename: Natalia
authors.initials: N
authors.lastname: Macchiaroli
authors.affiliation: Instituto de Investigaciones en Microbiología y Parasitología Médicas (IMPaM), Facultad de Medicina, Universidad de Buenos Aires (UBA)-Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Buenos Aires, Argentina.
authors.forename: Lucas L
authors.initials: LL
authors.lastname: Maldonado
authors.affiliation: Parasite Genomics Group, Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Zarowiecki
authors.affiliation: Instituto de Investigaciones en Microbiología y Parasitología Médicas (IMPaM), Facultad de Medicina, Universidad de Buenos Aires (UBA)-Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Buenos Aires, Argentina.
authors.forename: Marcela
authors.initials: M
authors.lastname: Cucher
authors.affiliation: Instituto de Biotecnología, CICVyA, INTA, Hurlingham, Argentina.
authors.forename: María Inés
authors.initials: MI
authors.lastname: Gismondi
authors.affiliation: Instituto de Investigaciones en Microbiología y Parasitología Médicas (IMPaM), Facultad de Medicina, Universidad de Buenos Aires (UBA)-Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Buenos Aires, Argentina.
authors.forename: Laura
authors.initials: L
authors.lastname: Kamenetzky
authors.affiliation: Instituto de Investigaciones en Microbiología y Parasitología Médicas (IMPaM), Facultad de Medicina, Universidad de Buenos Aires (UBA)-Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET), Buenos Aires, Argentina. Electronic address: mrosenzvit@fmed.uba.ar.
authors.forename: Mara Cecilia
authors.initials: MC
authors.lastname: Rosenzvit
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D004446:Echinococcus / Q000235:genetics* / Q000254:growth & development*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D017238:Genes, Helminth; D023281:Genomics; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D017423:Sequence Analysis, RNA; D013621:Taenia / Q000235:genetics / Q000254:growth & development
chemical_list: D020413:3' Untranslated Regions; D035683:MicroRNAs
keywords: 3′UTRs; Development; Echinococcus; MicroRNA; Parasite; Target