Abstract
Extracellular vesicles (EV) are secretory membranous elements used by cells to transport proteins, lipids, mRNAs, and microRNAs (miRNAs). While their existence has been known for many years, only recently has research begun to identify their function in intercellular communication and gene regulation. Importantly, cells have the ability to selectively sort miRNA into EVs for secretion to nearby or distant targets. These mechanisms broadly include RNA-binding proteins such as hnRNPA2B1 and Argonaute-2, but also membranous proteins involved in EV biogenesis such as Caveolin-1 and Neural Sphingomyelinase 2. Moreover, certain disease states have also identified dysregulated EV-miRNA content, shedding light on the potential role of selective sorting in pathogenesis. These pathologies include chronic lung disease, immune response, neuroinflammation, diabetes mellitus, cancer, and heart disease. In this review, we will overview the mechanisms whereby cells selectively sort miRNA into EVs and also outline disease states where EV-miRNAs become dysregulated.
Highlights
Extracellular vesicles (EV) are a broad group of membranous vesicles classified based on size, function, RNA profiles, or method of biogenesis
MVs, and apoptotic bodies (ABs) are all generated via independent mechanisms, but all are known to contain miRNAs
In order to selectively sort miRNA, RNA-binding protein (RBP) such as hnRNPA2B1, Ago2, Y-Box Binding Protein 1 (YBX-1), MEX3C, Major vault protein (MVP), and the La protein all appear to bind miRNAs and facilitate their transfer into EVs. For many of these RBPs, the literature has recently begun to identify specific miRNA-binding motifs capable of exerting selectivity over the miRNAs shuttled into EVs
Summary
EVs are a broad group of membranous vesicles classified based on size, function, RNA profiles, or method of biogenesis. Regardless of the subtype, EVs are gaining increased attention for their function in transporting both proteins and RNA extracellularly for wide-ranging effects [2,3] This exosome-mediated transfer of mRNA and microRNA (miRNA) has been shown to induce effects on recipient cells, such as regulate protein expression, suggesting an in vivo functional role of exosome-derived mRNA and miRNA [4]. Certain populations of miRNA-rich EVs have been identified that represent 6% of the total EVs but approximately 39% of the total EV-derived RNA [8] This evidence supports the concept that miRNAs can be selectively sorted into EVs through a purposeful rather than passive process. We will discuss the effect of certain disease states such as heart disease and diabetes mellitus (DM) on miRNA packaging
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