Mechanisms of RNA loading into exosomes

Abstract

a b s t r a c tUpon fusion of multivesicular bodies (MVBs) with the plasma membrane, intraluminal vesicles (ILVs) are released into the extracellular space as exosomes. Since the lipid composition of the exosomal membrane resembles that of raft microdomains, the inward budding process involves the raft-like region of the MVB limiting membrane. Although published research suggests that cellular RNAs may be selectively sorted into exosomes, the molecular mechanisms remain elusive. In this review, we suggest that there is a continuous interaction of cellular RNAs with the outer (cytoplasmic) surface of MVBs and that the selection for incorporation of these RNAs into ILVs is based on their affinity to the raft-like region in the outer layer of the MVB membrane.

Extracellular vesicle isolation and characterization: toward clinical application

“…Numerous proteins found exclusively in sMVs (e.g., KIF23, RACGAP1, chromosome segregation 1-like protein, exportin-2 [CSE1L/CAS]) warrant further study as to their potential use as discriminatory markers for sMVs. The high abundance of RNA binding proteins such as the family of heterogeneous nuclear ribonucleoproteins (hnRNPs) in both EV subtypes is consistent with their proposed role in selective loading of RNA cargoes (106). This study is a first attempt at defining protein markers that would allow discrimination between exosomes and sMVs; however, this study was restricted to human colon cancer cell lines and the dog kidney MDCK cell line.…”

Uptake and impact of natural diet-derived small RNA in invertebrates: Implications for ecology and agriculture

“…104 First, miRNAs can be delivered by a wide variety of lipid-bound vesicles, including exosomes in a wide range of biological processes. [105][106][107][108][109][110][111][112] miRNA sorting into exosomes can be influenced by a number of factors, 113 including dose, 114 3 0 end uridylation, 115 nucleotide sequence motifs, 116 interaction with RNA-binding proteins, 117,118 and localization to GW bodies. 119 Second, miRNAs can be incorporated into a variety of ribonucleoprotein complexes, including those containing ARGONAUTE family members, [120][121][122] HDL, 123,124 and HuR.…”

Stem cell-derived exosomes: a novel vector for tissue repair and diabetic therapy

“…The endosomal sorting complexes required for transport (ESCRT) pathway is believed to play a principal role in this process (Bobrie et al 2011, Colombo et al 2013, Cocucci & Meldolesi 2015. There is also evidence of an ESCRT-independent cargo sorting mechanism requiring ceramide believed to govern the packaging of RNA and certain proteins (Colombo et al 2013, Schneider & Simons 2013, Janas et al 2015. The cargo sorting mechanisms of exosomes are believed to be highly selective as evidenced by the large expression overlap between exosomes of different cellular origins (Guduric-Fuchs et al 2012).…”