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Axonal precursor mi RNA s hitchhike on endosomes and locally regulate the development of neural circuits
Author(s) -
Corradi Eloina,
Dalla Costa Irene,
Gavoci Antoneta,
Iyer Archana,
Roccuzzo Michela,
Otto Tegan A,
Oliani Eleonora,
Bridi Simone,
Strohbuecker Stephanie,
SantosRodriguez Gabriela,
Valdembri Donatella,
Serini Guido,
AbreuGoodger Cei,
Baudet MarieLaure
Publication year - 2020
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.2019102513
Subject(s) - biology , endosome , rna , microbiology and biotechnology , biological neural network , neuroscience , genetics , gene , intracellular
Various species of non‐coding RNA s (ncRNAs) are enriched in specific 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 micro RNA s (pre‐mi RNA s) are actively trafficked to distal axons by hitchhiking primarily on late endosomes/lysosomes. Upon exposure to the axon guidance cue semaphorin 3A (Sema3A), pre‐mi RNA s are processed specifically within axons into newly generated mi RNA s, one of which, in turn, silences the basal translation of tubulin beta 3 class III ( TUBB 3), but not amyloid beta precursor protein (APP). At the organismal level, these mature mi RNA s are required for growth cone steering and a fully functional visual system. Overall, our results uncover a novel mode of nc RNA transport from one cytosolic compartment to another within polarized cells. They also reveal that newly generated mi RNA s are critical components of a nc RNA ‐based signaling pathway that transduces environmental signals into the structural remodeling of subcellular compartments.