The pervasive occurrence of cell-free miRNAs in circulation suggests that these species play an emerging role as regulatory molecules in the secretory environment. Are these molecules released fortuitously with no clear biological intent? Or do they constitute a regulatory architecture that has evolved to modulate gene expression using the highways and byways of the circulatory system? The study of circulating miRNAs continues to increase our understanding of the regulation of genomes. The diversity of acellular miRNAs from a functional perspective is discussed, and in particular we explore their utility in a clinical setting as blood-based biomarkers for diseases. WIREs RNA 2013, 4:129–138. doi: 10.1002/wrna.1149
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Conflict of interest: The authors declare no conflict of interest.