RT Journal Article SR Electronic T1 MicroRNA exocytosis by large dense-core vesicle fusion JF bioRxiv FD Cold Spring Harbor Laboratory SP 093278 DO 10.1101/093278 A1 Alican Gümürdü A1 Ramazan Yildiz A1 Erden Eren A1 Gökhan Karakülah A1 Turgay Ünver A1 Şermin Genç A1 Yongsoo Park YR 2017 UL http://biorxiv.org/content/early/2017/03/08/093278.abstract AB 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.One Sentence Summary Using next-generation sequencing (NGS) for microRNA (miRNA) and synthetic neurotransmission, we observed that large dense-core vesicles (LDCVs) contain a variety of miRNA together with classical neurotransmitters, and that miRNA can be released by vesicle fusion mediated by SNARE.