Extracellular miRNAs and cell-cell communication: problems and prospects
MicroRNAs (miRNAs) are short RNA molecules regulating multiple cellular processes through posttranscriptional gene silencing. Over the last decade, miRNA have been found in extracellular space and have been consistently shown to mediate functional communication between cells. While it remains widely accepted that miRNA transfer between cells occurs via extracellular vesicles (EVs), multiple other carriers of cell-free miRNA have been described. In addition, some studies have demonstrated that both miRNA and their binding partners, Argonaute proteins, remain hardly detectable in common isolates of EVs. In this work, we summarize the state-of-the-art mechanisms of miRNA sorting and secretion, discuss methodological challenges associated with extracellular miRNA research, and suggest experimental steps to resolve current inconsistencies in the field of miRNA-mediated cell-cell communication.