MicroRNA Exocytosis by Vesicle Fusion in Neuroendocrine Cells

Abstract

MicroRNAs (miRNAs) are short non-coding RNAs that posttranscriptionally regulate gene expression inside the cell. Extracellular circulating miRNAs are also observed outside the cell, but their origin is poorly understood. Recently, miRNA has been shown to be exocytosed by vesicle fusion; this observation demonstrates that vesicle-free miRNAs are secreted from neuroendocrine cells, in a manner similar to hormone secretion. miRNAs are stored in large dense-core vesicles together with catecholamines, then released by vesicle fusion in response to stimulation; in this way, vesicle-free miRNA may regulate cell-to-cell communication including the regulation of gene expression and cellular signaling. Therefore, miRNA has been suggested to function as a hormone; i.e., a ribomone (ribonucleotide + hormone). This review focuses on the mechanisms by which vesicle-free miRNAs are secreted from neuroendocrine cells and will discuss potential functions of vesicle-free miRNAs and how vesicle-free miRNAs regulate cell-to-cell communication.

Neuronal extracellular microRNAs miR‐124 and miR‐9 mediate cell–cell communication between neurons and microglia

“…This finding implies that spontaneous electric activity of neurons was important for miRNA secretion. Electric activity of neurons is known to increase exocytosis (Chivet et al, ; Park, ), and also facilitate opening of voltage‐gated channel proteins that might also directly and/or indirectly contribute to the release of ECmiRNAs. This is quite an interesting and important finding, which will be further investigated in the future.…”

Extracellular Vesicles and the Stress System

“…DCVs in the CNS are primarily peptidergic vesicles (LDCVs), packaging neuropeptides and peptide hormones [117, 118]. In addition, LDCVs may co-store monoamines, neurotrophic factors, ATP, miRNAs as well as pre-assembled components that need to be transferred to synaptic active zones [119, 120]. Neuropeptides are the most diverse and most numerous signaling molecules in the brain, acting as neurotransmitters, neuromodulators and neurohormones.…”

“…Of note, neuropeptides that act as neuromodulators may activate receptors all along the target cells [118]. LDCVs often contain multiple neuropeptides, the latter being sorted into different LDCVs in the same cells [119, 121, 122]. In addition, LDCVs are enriched with miRNAs (∼60% of LDCV RNA content) [119], which are released via SNARE-mediated exocytosis in a Ca ++ -dependent manner [122].…”

“…LDCVs often contain multiple neuropeptides, the latter being sorted into different LDCVs in the same cells [119, 121, 122]. In addition, LDCVs are enriched with miRNAs (∼60% of LDCV RNA content) [119], which are released via SNARE-mediated exocytosis in a Ca ++ -dependent manner [122]. Of note, the miRNA concentration in LDCVs is comparable to that of neuropeptides.…”

Detectability of circulating microRNAs in microRNA extracts with low purity and yield using quantitative real-time polymerase chain reaction: Supporting evidence

“…7,8 miRNAs are transported out from cells mainly by exocytosis, and they are either encapsulated in or free from vesicles for cell-cell communication. 9 A growing body of evidence demonstrates the promising utility of circulating miRNAs as biomarkers of noncommunicable diseases, but their pre-analytical processing and detection still suffer from several challenges. 10 Despite the good number of scientific publications about issues and improvements in certain pre-analytical parts for the study of circulating miRNAs, such as sample processing and circulating miRNA extraction, no study has reported the suitability of utilizing circulating miRNA extracts with low purity and yield in detecting miRNA using quantitative realtime polymerase chain reaction (qPCR).…”