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.
Highlights
MicroRNAs are a class of small non-coding RNAs that are ~22 nucleotides in length; they downregulate translation of target mRNA [1, 2]. ncRNAs are transcribed from the genome, but not translated to protein; ~98% of RNA transcripts in humans are non-coding [3]
Large dense-core vesicles in chromaffin cells contain miRNAs, which are released in response to stimulation, together with catecholamines and peptides. miRNA exocytosis by the soluble N-ethylmaleimidesensitive factor attachment protein receptor (SNARE) complex and Syt-1 has been discovered in chromaffin cells and additional secreted vesicle-free miRNAs are expected to be discovered. miRNAs have hormone-like activities; i.e., they are secreted from neuroendocrine cells, spread through the blood stream, and regulate target cells by gene expression and/or cellular signaling
This activity of secreted miRNAs is opening an exciting research area in RNA biology, endocrinology, and neuroscience, but several important questions remain unanswered, including: [1] what are the physiological functions of secreted and vesicle-free miRNAs? It becomes clear that miRNA are secreted by vesicle fusion, but there is little evidence showing the functions of these secreted miRNAs
Summary
Reviewed by: Maria-Dolors Piulachs, Consejo Superior de Investigaciones Científicas (CSIC), Spain. MicroRNAs (miRNAs) are short non-coding RNAs that posttranscriptionally regulate gene expression inside the cell. Extracellular circulating miRNAs are observed outside the cell, but their origin is poorly understood. 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, 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. MiRNA has been suggested to function as a 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
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