title: MicroRNA exocytosis by large dense-core vesicle fusion.
abstract: Neurotransmitters and peptide hormones are secreted into outside the cell by a vesicle fusion process. Although non-coding RNA (ncRNA) that include microRNA (miRNA) regulates gene expression inside the cell where they are transcribed, extracellular miRNA has been recently discovered outside the cells, proposing that miRNA might be released to participate in cell-to-cell communication. Despite its importance of extracellular miRNA, the molecular mechanisms by which miRNA can be stored in vesicles and released by vesicle fusion remain enigmatic. Using next-generation sequencing, vesicle purification techniques, and synthetic neurotransmission, we observe that large dense-core vesicles (LDCVs) contain a variety of miRNAs including miR-375. Furthermore, miRNA exocytosis is mediated by the SNARE complex and accelerated by Ca2+. Our results suggest that miRNA can be a novel neuromodulator that can be stored in vesicles and released by vesicle fusion together with classical neurotransmitters.
authors.affiliation: Izmir International Biomedicine and Genome Institute (iBG-izmir), Dokuz Eylül University, 35340, Izmir, Turkey.|Department of Neuroscience, Health Science Institute, Dokuz Eylül University, 35340, Izmir, Turkey.
authors.forename: Alican
authors.initials: A
authors.lastname: Gümürdü
authors.affiliation: Izmir International Biomedicine and Genome Institute (iBG-izmir), Dokuz Eylül University, 35340, Izmir, Turkey.|Department of Neuroscience, Health Science Institute, Dokuz Eylül University, 35340, Izmir, Turkey.
authors.forename: Ramazan
authors.initials: R
authors.lastname: Yildiz
authors.affiliation: Izmir International Biomedicine and Genome Institute (iBG-izmir), Dokuz Eylül University, 35340, Izmir, Turkey.|Department of Neuroscience, Health Science Institute, Dokuz Eylül University, 35340, Izmir, Turkey.
authors.forename: Erden
authors.initials: E
authors.lastname: Eren
authors.affiliation: Izmir International Biomedicine and Genome Institute (iBG-izmir), Dokuz Eylül University, 35340, Izmir, Turkey.
authors.forename: Gökhan
authors.initials: G
authors.lastname: Karakülah
authors.affiliation: Izmir International Biomedicine and Genome Institute (iBG-izmir), Dokuz Eylül University, 35340, Izmir, Turkey.
authors.forename: Turgay
authors.initials: T
authors.lastname: Ünver
authors.affiliation: Izmir International Biomedicine and Genome Institute (iBG-izmir), Dokuz Eylül University, 35340, Izmir, Turkey.|Department of Neuroscience, Health Science Institute, Dokuz Eylül University, 35340, Izmir, Turkey.
authors.forename: Şermin
authors.initials: Ş
authors.lastname: Genç
authors.affiliation: Izmir International Biomedicine and Genome Institute (iBG-izmir), Dokuz Eylül University, 35340, Izmir, Turkey.
authors.forename: Yongsoo
authors.initials: Y
authors.lastname: Park
mesh_terms: D000818:Animals; D002417:Cattle; D005089:Exocytosis; D008561:Membrane Fusion; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D008954:Models, Biological; D016716:PC12 Cells; D051381:Rats; D022142:Secretory Vesicles / Q000378:metabolism*; D017423:Sequence Analysis, RNA; D050988:Vesicle-Associated Membrane Protein 2 / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D050988:Vesicle-Associated Membrane Protein 2