MicroRNA Passenger Strand
Orchestral Symphony of Paracrine Signaling
During the past few years, increasing studies have identified microRNAs to be present in the circulation, either encapsulated in microvesicles or exosomes or associated with RNA-binding proteins or lipoproteins.1 Recent studies have suggested that circulating microRNAs may function in cell–cell communication, being transported from one cell type to another and regulating target gene expression in recipient cells.2,3 Although it has been generally thought that the passenger strand of the microRNA duplex is degraded during microRNA biogenesis and only the guide strand of the microRNA duplex is selected to become the mature functional microRNA, there is mounting evidence that passenger strand microRNAs can also target mRNAs and have biological functions in pathologies such as cancer.4,5 In the current study, Bang et al6 present evidence that exosomes produced by cardiac fibroblasts contain passenger strand microRNAs, which are transferred to cardiomyocytes and play a role in the development of fibroblast-derived cardiomyocyte hypertrophy, revealing a novel method of paracrine communication between cardiac fibroblasts and cardiomyocytes.
How Was the Hypothesis Tested?
The authors6 used electron microscopy to demonstrate the ability of neonatal rat cardiac fibroblasts to produce and secrete exosomes (fibroblast-derived exosomes). They further confirmed the identity of the exosomes by performing Western blotting and fluorescence-activated cell sorting analyses for the presence of an exosomal marker protein. To assess the microRNA content of fibroblast-derived exosomes, the authors used a microRNA …