title: Profiling of small RNA cargo of extracellular vesicles shed by Trypanosoma cruzi reveals a specific extracellular signature.
abstract: Over the last years, an expanding family of small regulatory RNAs (e.g. microRNAs, siRNAs and piRNAs) was recognized as key players in novel forms of post-transcriptional gene regulation in most eukaryotes. However, the machinery associated with Ago/Dicer-dependent small RNA biogenesis was thought to be either entirely lost or extensively simplified in some unicellular organisms including Trypanosoma cruzi, Saccharomyces cerevisiae, Leishmania major and Plasmodium falciparum. Although the biogenesis of small RNAs from non-coding RNAs represent a minor fraction of the normal small RNA transcriptome in eukaryotic cells, they represent the unique small RNA pathways in Trypanosoma cruzi which produce different populations of small RNAs derived from tRNAs, rRNAs, sn/snoRNAs and mRNAs. These small RNAs are secreted included in extracellular vesicles and transferred to other parasites and susceptible mammalian cells. This process represents a novel form of cross-kingdom transfer of genetic material suggesting that secreted vesicles could represent new relevant pieces in life cycle transitions, infectivity and cell-to-cell communication. Here, we provide for the first time a detailed analysis of the small RNA cargo of extracellular vesicles from T. cruzi epimastigotes under nutritional stress conditions compared to the respective intracellular compartment using deep sequencing. Compared with the intracellular compartment, shed extracellular vesicles showed a specific extracellular signature conformed by distinctive patterns of small RNAs derived from rRNA, tRNA, sno/snRNAs and protein coding sequences which evidenced specific secretory small RNA processing pathways.
authors: Bioinformatics Unit, Institut Pasteur de Montevideo, Mataojo 2020, Montevideo 11400, Uruguay.
authors: Tamara
authors: T
authors: Fernandez-Calero
authors: Functional Genomics Unit, Institut Pasteur de Montevideo, Mataojo 2020, Montevideo 11400, Uruguay.
authors: Rosa
authors: R
authors: Garcia-Silva
authors: Bioinformatics Unit, Institut Pasteur de Montevideo, Mataojo 2020, Montevideo 11400, Uruguay.
authors: Alvaro
authors: A
authors: Pena
authors: Molecular Biology Unit, Institut Pasteur de Montevideo, Mataojo 2020, Montevideo 11400, Uruguay.
authors: Carlos
authors: C
authors: Robello
authors: Division of Oncology, Department of Clinical Sciences, Lund University Cancer Center, Lund 223 81, Sweden.
authors: Helena
authors: H
authors: Persson
authors: Division of Oncology, Department of Clinical Sciences, Lund University Cancer Center, Lund 223 81, Sweden.
authors: Carlos
authors: C
authors: Rovira
authors: Bioinformatics Unit, Institut Pasteur de Montevideo, Mataojo 2020, Montevideo 11400, Uruguay.
authors: Hugo
authors: H
authors: Naya
authors: Functional Genomics Unit, Institut Pasteur de Montevideo, Mataojo 2020, Montevideo 11400, Uruguay; Department of Medicine, Faculty of Medicine, Universidad de la República, Av Gral Flores 2125, Montevideo 11800, Uruguay. Electronic address: cayota@pasteur.edu.uy.
authors: Alfonso
authors: A
authors: Cayota
mesh_terms: D000067128:Extracellular Vesicles / Q000737:chemistry*; D059014:High-Throughput Nucleotide Sequencing; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D016053:RNA, Protozoan / Q000032:analysis* / Q000235:genetics; D012335:RNA, Ribosomal / Q000032:analysis / Q000235:genetics; D012342:RNA, Small Nuclear / Q000032:analysis / Q000235:genetics; D012343:RNA, Transfer / Q000032:analysis / Q000235:genetics; D014349:Trypanosoma cruzi / Q000235:genetics / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D016053:RNA, Protozoan; D012335:RNA, Ribosomal; D012342:RNA, Small Nuclear; D012343:RNA, Transfer
keywords: Extracellular vesicles; Small non-coding RNA; Small rDNA-derived fragments; Trypanosoma cruzi; tRNA-derived fragments