title: Deep sequencing of RNA from immune cell-derived vesicles uncovers the selective incorporation of small non-coding RNA biotypes with potential regulatory functions.
abstract: Cells release RNA-carrying vesicles and membrane-free RNA/protein complexes into the extracellular milieu. Horizontal vesicle-mediated transfer of such shuttle RNA between cells allows dissemination of genetically encoded messages, which may modify the function of target cells. Other studies used array analysis to establish the presence of microRNAs and mRNA in cell-derived vesicles from many sources. Here, we used an unbiased approach by deep sequencing of small RNA released by immune cells. We found a large variety of small non-coding RNA species representing pervasive transcripts or RNA cleavage products overlapping with protein coding regions, repeat sequences or structural RNAs. Many of these RNAs were enriched relative to cellular RNA, indicating that cells destine specific RNAs for extracellular release. Among the most abundant small RNAs in shuttle RNA were sequences derived from vault RNA, Y-RNA and specific tRNAs. Many of the highly abundant small non-coding transcripts in shuttle RNA are evolutionary well-conserved and have previously been associated to gene regulatory functions. These findings allude to a wider range of biological effects that could be mediated by shuttle RNA than previously expected. Moreover, the data present leads for unraveling how cells modify the function of other cells via transfer of specific non-coding RNA species.
authors: Department of Biochemistry & Cell Biology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 2, 3584 CM Utrecht, The Netherlands. e.n.m.nolte@uu.nl
authors: Esther N M
authors: EN
authors: Nolte-'t Hoen
authors: Henk P J
authors: HP
authors: Buermans
authors: Maaike
authors: M
authors: Waasdorp
authors: Willem
authors: W
authors: Stoorvogel
authors: Marca H M
authors: MH
authors: Wauben
authors: Peter A C
authors: PA
authors: 't Hoen
mesh_terms: D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000737:chemistry / Q000276:immunology; D059014:High-Throughput Nucleotide Sequencing; D035683:MicroRNAs / Q000032:analysis / Q000737:chemistry; D058727:RNA, Small Untranslated / Q000032:analysis* / Q000737:chemistry / Q000502:physiology; D012343:RNA, Transfer / Q000032:analysis / Q000737:chemistry; D012091:Repetitive Sequences, Nucleic Acid; D017423:Sequence Analysis, RNA; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology; D022161:Transport Vesicles / Q000737:chemistry*
chemical_list: D035683:MicroRNAs; D058727:RNA, Small Untranslated; D012343:RNA, Transfer