Abstract

Since their discovery in the mid-1990s, microRNAs (miRNAs) have captured the attention of the scientific community by their ability to post-transcriptionally and subtly regulate a large but still poorly defined set of gene targets and to control most cellular and molecular processes, making them central effectors of gene reprogramming and cell functioning under both normal and pathophysiological conditions. In this mini-review we summarize step by step the molecular mechanisms involved in miRNA biogenesis and mRNA regulation, the latter depending directly on the duration of the miRNA-mediated translational arrest and the integrity of the transcript extremities. We also discuss the nomenclature of miRNAs, the pairing rules between a miRNA and its target through the seed sequence, and the remarkable complexity of the interactions between thousands of genes and miRNAs in a cell at the origin of a regulatory and communicative network that intriguingly evokes the neuronal interconnections occurring in the brain. We recall that miRNAs are not only intracellular gene regulators but also trans-communicators capable of operating remotely from their production site in blood-circulating macrovesicles or exosomes. We stress their role in tissue carcinogenesis and their use as antitumoral agents with two examples of miRNAs that have reached the clinic but with various successes. Finally, we conclude by stating that despites the many obstacles to be overcome, miRNAs remain major candidates for therapeutic use in cancer and therefore, the scientific community should continue its efforts to pursue investigations in the field of miRNA to develop intelligent, safe and controllable systems and vectors for miRNA delivery.