Since the discovery of the first microRNA (miRNA) almost 20 years ago, insight into their functional role has gradually been accumulating. This class of non-coding RNAs has recently been implicated as key molecular regulators in the biology of most eukaryotic cells, contributing to the physiology of various systems including immune, cardiovascular, nervous systems and also to the pathophysiology of cancers. Interestingly, Semaphorins, a class of evolutionarily conserved signalling molecules, are acknowledged to play major roles in these systems also. This, combined with the fact that Semaphorin signalling requires tight spatiotemporal regulation, a hallmark of miRNA expression, suggests that miRNAs could be crucial regulators of Semaphorin function. Here, we review evidence suggesting that Semaphorin signalling is regulated by miRNAs in various systems in health and disease. In particular, we focus on neural circuit formation, including axon guidance, where Semaphorin function was first discovered.
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