Abstract
Post-transcriptional regulation of messenger RNA (mRNA) metabolism and subcellular localization is of the utmost importance both during development and in cell differentiation. Besides carrying genetic information, mRNAs contain cis-acting signals (zip codes), usually present in their 5′- and 3′-untranslated regions (UTRs). By binding to these signals, trans-acting factors, such as RNA-binding proteins (RBPs), and/or non-coding RNAs (ncRNAs), control mRNA localization, translation and stability. RBPs can also form complexes with non-coding RNAs of different sizes. The release of extracellular vesicles (EVs) is a conserved process that allows both normal and cancer cells to horizontally transfer molecules, and hence properties, to neighboring cells. By interacting with proteins that are specifically sorted to EVs, mRNAs as well as ncRNAs can be transferred from cell to cell. In this review, we discuss the mechanisms underlying the sorting to EVs of different classes of molecules, as well as the role of extracellular RNAs and the associated proteins in altering gene expression in the recipient cells. Importantly, if, on the one hand, RBPs play a critical role in transferring RNAs through EVs, RNA itself could, on the other hand, function as a carrier to transfer proteins (i.e., chromatin modifiers, and transcription factors) that, once transferred, can alter the cell’s epigenome.
Highlights
The release of extracellular vesicles (EVs) by a producing cell and their fusion with surrounding, recipient cells is probably an ancient process
These analyses are difficult, because it has been found that the same cell type can produce vesicles with different contents depending on the different signals received from the environment; for example, it has been demonstrated that colon cancer cells secrete two exosome populations, with different protein contents, from the basolateral, and the apical side, respectively [5,51], and this finding might be valid for all cells with polarity
These results suggest that post-transcriptional modifications could contribute to RNA sorting to EVs
Summary
The release of extracellular vesicles (EVs) by a producing cell and their fusion with surrounding, recipient cells is probably an ancient process. It is, highly conserved in evolution from bacteria [1,2] to human cells [3], and, most importantly, there is evidence of inter-specific transfer of EVs, even from microorganisms to mammal cells [4]. MiRNAs may target the mRNAs of the recipient cells, decreasing their translation and/or increasing their degradation, depleting cells of specific resident proteins [10]. Coming back to EVs, both coding and non-coding RNAs in vesicles could act as protein carriers that transport proteins from one cell to another; once in the recipient cells, these proteins may bind and modify chromatin structure and activity, acting as epigenetic players able to modify gene expression. EVs seem to have in cancer [14], and of the apparent ‘infectious’ potential attributed to them in some neurodegenerative diseases [15]
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