Y-box protein 1 is required to sort microRNAs into exosomes in cells and in a cell-free reaction

Human cells release molecules into their surroundings via membrane-bound packets called exosomes. These molecules can then circulate throughout the body and are protected from degradation. Among the cargos carried by exosomes are small molecules of RNA known as microRNAs, which are involved in regulating gene activity. Only a select subset of the hundreds of microRNAs in a human cell end up packaged into exosomes. This suggests that there might be a specific mechanism that sorts those microRNAs that are destined for export. However, few proteins or other factors that might be involved in this sorting process had been identified to date. Shurtleff et al. set out to identify these factors and started by purifying exosomes from human cells grown in the laboratory and looking for microRNAs that were more abundant in the exosomes than the cells. One exosome-specific microRNA, called miR-223, was further studied via a test-tube based system that uses extracts from cells rather than cells themselves. These experiments confirmed that miR-223 is selectively packed into exosomes that formed in the test tube. Using this system, Shurtleff et al. then isolated a protein called Y-box Protein I (or YBX1 for short) that binds to RNA molecules and found that it was required for this selective packaging. YBX1 is known to be a constituent of exosomes released from intact cells and may therefore be required to sort other RNA molecules into exosomes. Future studies will explore how YBX1 recognizes those RNA molecules to be exported from cells via exosomes. Also, because exosomes have been implicated in some diseases such as cancer, it will be important to explore what role exosome-specific microRNAs play in both health and disease.