Precursor miRNAs are trafficked along axons associated with vesicles and locally processed to regulate growth cone steering

Eloina Corradi, Antoneta Gavoci, Stephanie Strohbuecker, Michela Roccuzzo, Irene Dalla Costa, Archana Iyer, Simone Bridi, Gabriela Santoz Rodriguez, Cei Abreu-Goodger, Marie-Laure Baudet

Research output: Working paper

Abstract / Description of output

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.
Original languageEnglish
PublisherbioRxiv, at Cold Spring Harbor Laboratory
Number of pages42
DOIs
Publication statusPublished - 14 Nov 2018

Keywords / Materials (for Non-textual outputs)

  • axon
  • growth cone
  • brain wriing
  • axon guidance
  • pathfinding
  • vision
  • retinal ganglion cells
  • RGCs
  • Xenopus
  • retina
  • miRNAs
  • precursor miRNAs
  • pre-miRNAs
  • tubulin beta 3 class III
  • TUBB3
  • amyloid beta precursor protein
  • APP
  • THBS1
  • miR-181
  • pre-miR-181a-1
  • CD63
  • vesicle
  • late endosome
  • multivesicular bodies
  • MVB
  • lysosome
  • local translation
  • RNA transport
  • RNA localization
  • compartment

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