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♦ See referenced article, J. Biol. Chem. 2010, 285, 17442–17452
MicroRNAs are key regulators of gene expression, and the presence of circulating miRNAs in the blood suggests they could be useful biomarkers of different diseases including cancer. However, almost nothing is known about the machinery involved in the secretion of miRNAs or the biological function of circulating miRNAs. In this Paper of the Week, Nobuyoshi Kosaka and colleagues demonstrated that miRNA secretion is regulated by neutral sphingomyelinase 2, the rate-limiting enzyme of ceramide synthesis. They also demonstrated that although ceramide-mediated secretion involves miRNA packaging into exosomes, the process does not require the ESCRT (endosomal sorting complex required for transport) machinery. Perhaps most interestingly, Kosaka and colleagues found that cell media enriched with secreted miR-146a (which is tumor-suppressive) could illicit gene-silencing effects in recipient cells, indicating that miRNA activity is transferable to other cells. Many questions still remain regarding miRNA secretion, but these thorough studies present the first unambiguous identification of a component of the miRNA secretion machinery and thus are of exceptional significance in miRNA research.