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

Eloina Corradi, Antoneta Gavoci, Stephanie Strohbuecker, Michela Rocuzzo, Irene Dalla Costa, Archana Iyer, Simone Bridi, Gabriela Santoz Rodriguez, Cei Abreu-Goodger, Marie-Laure Baudet
doi: https://doi.org/10.1101/470393
Eloina Corradi
1Center for integrative biology (CIBIO), University of Trento, via Sommarive 9, Povo, Trento, Italy
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Antoneta Gavoci
1Center for integrative biology (CIBIO), University of Trento, via Sommarive 9, Povo, Trento, Italy
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Stephanie Strohbuecker
1Center for integrative biology (CIBIO), University of Trento, via Sommarive 9, Povo, Trento, Italy
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Michela Rocuzzo
1Center for integrative biology (CIBIO), University of Trento, via Sommarive 9, Povo, Trento, Italy
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Irene Dalla Costa
1Center for integrative biology (CIBIO), University of Trento, via Sommarive 9, Povo, Trento, Italy
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Archana Iyer
1Center for integrative biology (CIBIO), University of Trento, via Sommarive 9, Povo, Trento, Italy
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Simone Bridi
1Center for integrative biology (CIBIO), University of Trento, via Sommarive 9, Povo, Trento, Italy
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Gabriela Santoz Rodriguez
2Unidad de Genómica Avanzada (Langebio), Cinvestav, Irapuato 36821, Mexico
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Cei Abreu-Goodger
2Unidad de Genómica Avanzada (Langebio), Cinvestav, Irapuato 36821, Mexico
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Marie-Laure Baudet
1Center for integrative biology (CIBIO), University of Trento, via Sommarive 9, Povo, Trento, Italy
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Abstract

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.

Highlights

  • Precursor miRNAs are actively transported along axons to the growth cone tethered to CD63-positive vesicles

  • Sema3A but not Slit2 induces the local biogenesis of specific miRNAs within axons

  • Mature miRNAs are important for growth cone responsiveness ex vivo and the establishment of functional connections in vivo

  • Newly synthesized miRNAs inhibit the basal translation of TUBB3 but not APP upon Sema3A exposure

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted November 14, 2018.
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Precursor miRNAs are trafficked along axons associated with vesicles and locally processed to regulate growth cone steering
Eloina Corradi, Antoneta Gavoci, Stephanie Strohbuecker, Michela Rocuzzo, Irene Dalla Costa, Archana Iyer, Simone Bridi, Gabriela Santoz Rodriguez, Cei Abreu-Goodger, Marie-Laure Baudet
bioRxiv 470393; doi: https://doi.org/10.1101/470393
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Precursor miRNAs are trafficked along axons associated with vesicles and locally processed to regulate growth cone steering
Eloina Corradi, Antoneta Gavoci, Stephanie Strohbuecker, Michela Rocuzzo, Irene Dalla Costa, Archana Iyer, Simone Bridi, Gabriela Santoz Rodriguez, Cei Abreu-Goodger, Marie-Laure Baudet
bioRxiv 470393; doi: https://doi.org/10.1101/470393

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