PT - JOURNAL ARTICLE AU - Eloina Corradi AU - Antoneta Gavoci AU - Stephanie Strohbuecker AU - Michela Rocuzzo AU - Irene Dalla Costa AU - Archana Iyer AU - Simone Bridi AU - Gabriela Santoz Rodriguez AU - Cei Abreu-Goodger AU - Marie-Laure Baudet TI - Precursor miRNAs are trafficked along axons associated with vesicles and locally processed to regulate growth cone steering AID - 10.1101/470393 DP - 2018 Jan 01 TA - bioRxiv PG - 470393 4099 - http://biorxiv.org/content/early/2018/11/14/470393.short 4100 - http://biorxiv.org/content/early/2018/11/14/470393.full AB - Various species of non-coding RNAs (ncRNAs) are enriched in subcellular compartments but the mechanisms orchestrating their delocalization 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, anchored to CD63-positive vesicles, to distal axons along microtubules. Upon exposure to the chemotropic cue Sema3A, pre-miRNAs are processed specifically within axons into newly synthesized mature miRNAs, which, in turn, silence the basal translation of TUBB3 but not of 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 synthesized miRNAs are critical components of a ncRNA-based signaling pathway that transduces environmental signals into the structural remodelling of subcellular compartments.HighlightsPrecursor miRNAs are actively transported along axons to the growth cone tethered to CD63-positive vesiclesSema3A but not Slit2 induces the local biogenesis of specific miRNAs within axonsMature miRNAs are important for growth cone responsiveness ex vivo and the establishment of functional connections in vivoNewly synthesized miRNAs inhibit the basal translation of TUBB3 but not APP upon Sema3A exposure