The RNA binding protein SYNCRIP controls microRNAs sorting in exosomes

While recent evidence clearly showed that exosomal microRNAs (miRNAs) are able to modulate the cellular microenvironment and that exosomal RNA cargo selection is deregulated in pathological conditions, the mechanisms controlling RNAs sorting into extracellular vesicles are still poorly understood. We identified in hepatocytes the RNA-binding protein SYNCRIP (Synaptotagmin-binding Cytoplasmic RNA-Interacting Protein, hnRNP-Q or NSAP1) as a component of the exosomal machinery controlling microRNA sorting: SYNCRIP knock-down was found to impair sorting of miRNAs in exosomes. Furthermore, SYNCRIP directly binds to a subset of miRNAs enriched in exosomes sharing a common extra-seed sequence (hEXO motif). Notably, the hEXO motif was proven to have a role in the regulation of miRNA localization, since embedment of this motif into a poorlyexported miRNA enhances its loading into exosomes. This evidence provides new insights into the mechanisms of miRNA exosomal sorting process. Moreover, these findings open the way for the possible selective modification of the miRNAs exosomal cargo.