GSE124168
Axonal precursor miRNAs hitchhike on endosomes and locally regulate the development of neural circuits
Various species of non-coding RNAs (ncRNAs) are enriched in subcellular compartments but the mechanisms orchestrating their localization and their local functions remain largely unknown. We investigated both aspects using the elongating retinal ganglion cell axon and its tip, the growth cone, as models. We reveal that specific endogenous precursor microRNAs (pre-miRNAs) are actively trafficked to distal axons by hitchhiking primarily on late endosomes / lysosomes. Upon exposure to Sema3A, pre-miRNAs are processed specifically within axons into newly generated miRNAs, one of which, in turn, silences the basal translation of tubulin beta 3 class III (TUBB3) but not amyloid beta precursor protein (APP). At the organismal level, these mature miRNAs are required for growth cone steering and a fully functional visual system. Overall, our results uncover a novel mode of ncRNA transport from one cytosolic compartment to another within polarized cells. They also reveal that newly generated miRNAs are critical components of a ncRNA-based signaling pathway that transduces environmental signals into the structural remodelling of subcellular compartments. Overall design: Total RNA profile were obtained from isolated retinal ganglion cell axons from Xenopus laevis retinal eye cultures using RNA-sequencing