Mechanisms of RNA loading into exosomes

•Intraluminal vesicles (ILVs) are released into extracellular space as exosomes.•ILVs are formed via lipid-induced inward budding of multivesicular bodies (MVBs).•Cellular RNAs continuously interact with the cytoplasmic surface of MVBs.•The limiting membrane of MVBs contains raft-like regions.•RNA affinity to raft-like regions selects RNAs for incorporation into ILVs/exosomes. Upon 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.