Analysis of small EV proteomes reveals unique functional protein networks regulated by VAP-A.

Little is known about biogenesis mechanisms that underlie EV heterogeneity. This study explores the protein repertoire of a specific subset of EVs that we recently identified to be generated at ER MCS and that are highly enriched in RNAs. We find that proteins from several classes of RNA machineries, including spliceosomes, are downregulated in EVs purified from cells knocked down for the ER MCS linker protein VAP-A. These data suggest that dynamic regulation of these protein machineries at ER MCS are involved in the sorting of RNA-RBP complexes into EVs.