Introduction to Extracellular Vesicles – Biogenesis, RNA Cargo Selection, Content, Release, and Uptak

Extracellular vesicles are a heterogeneous group of membrane-limited vesicles loaded with various proteins, lipids, and nucleic acids. Release of extracellular vesicles from its cell of origin occurs either through the outward budding of the plasma membrane or through the inward budding of the endosomal membrane, resulting in the formation of multivesicular bodies, which release vesicles upon fusion with the plasma membrane. The release of vesicles can facilitate intercellular communication by contact with or by internalization of contents, either by fusion with the plasma membrane or by endocytosis into “recipient” cells. Although the interest in extracellular vesicle research is increasing, there are still no real standards in place to separate or classify the different types of vesicles. (read more…)

RNA loading mechanisms and RNA species found in EVs.

a A graphical representation of the different RNA species found in EVs including mRNA, miRNA, tRNA, rRNA, vault RNA, circRNA, Y RNA, lncRNA, and sncRNA. b Packaging of RNA within the lipid bilayer membrane is thought to protect it from RNase digestion once released into the extracellular environment. c Different mechanisms of mRNA and miRNA loading into EV as shown in the left panel include: the enrichment of miRNA in EVs due to cellular stress; hnRNPA2B1 binding to GAGG motif present miRNA; 3′ end uridylation of miRNAs/increasing nSMase2 activity resulting in miRNA loading; the abundance of miRNA target mRNA transcripts in the cell and the binding of miRNA to lipids associated with EVs. Loading of mRNA or mRNA fragments is based on the presence of zipcode sequence and association with miR1289. [Components in image derived from Servier Medical Art Powerpoint image bank (Servier 2016)]