Beyond the Bubble: A Debate on microRNA Sorting Into Extracellular Vesicles.

Over the past decade, a scientific field has been developed demonstrating microRNAs (miRNAs) to be actively sorted into extracellular vesicles via specific nucleotide motifs that interact with discrete RNA-binding proteins. These miRNAs are proposed to be transported into recipient cells in which they can regulate specific cellular pathways. This mechanism could have enormous potential in explaining how cells signal and regulate other cells nearby or at a distance. Tens of studies have built this theme of a regulated transport of miRNAs. However, some concerns exist about this field. Taken together, there are concerns of a lack of a consistent motif, RNA-binding protein, or preferential miRNA involved in this process. In this study, we provide an expert and extensive analysis of the field that makes the cases for and against an active sorting mechanism. We provide potential explanations on why there is a lack of agreement. Most importantly, we provide ideas on how to move this field forward with more rigor and reproducibility. It is hoped that by engaging in a scientific debate of the pros and cons of this field, more rigorous experiments can be performed to conclusively demonstrate this biological activity.