Exomeres and supermeres: monolithic or diverse?

Abstract

Extracellular vesicles (EVs), including exosomes and microvesicles, are far from beingthe only RNA-containing extracellular particles (EPs). Recently, new 35-nm-sized EPswere discovered by asymmetric-flow field-flow ractionation and termed ‘exomeres’.Purification of exomeres was later performed by differential ltracentrifugation aswell. More recently, the supernatant of the high-speed ultracentrifugation used tocollect exomeres was further centrifuged to collect a new class of EP, termed ‘super-meres’. Supermeres contain high quantities of extracellular RNA and are enrichedin miR-1246. They are also replete in disease biomarkers and can induce metabolicand adaptive changes in recipient cells. Here, we reanalysed proteomic and tran-scriptomic data obtained in this exciting study to obtain further insights into themolecular composition of exomeres and supermeres. We found that the top-rankingRNAs in supermeres correspond to the footprints of extracellular protein complexes.These complexes protect fragments of the small nuclear RNA U2 and the 28S rRNAfrom extracellular ribonucleases (exRNases). We suggest that intracellular nanoparti-cles such as the U2 ribonucleoprotein, ribosomes and LGALS3BP ring-like decamersare released into the extracellular space. These heterogeneous EPs might be furtherprocessed by exRNases and co-isolate by ultracentrifugation with other componentsof exomeres and supermeres. We look forward to continuing progress in defin-ing exRNA carriers, bridging process definitions with molecular composition andfunction.