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EMBO J January 1, 2020; 39 (6): e102513.
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Axonal precursor miRNAs hitchhike on endosomes and locally regulate the development of neural circuits.

Corradi E , Dalla Costa I , Gavoci A , Iyer A , Roccuzzo M , Otto TA , Oliani E , Bridi S , Strohbuecker S , Santos-Rodriguez G , Valdembri D , Serini G , Abreu-Goodger C , Baudet ML .

Various species of non-coding RNAs (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 microRNAs (pre-miRNAs) are actively trafficked to distal axons by hitchhiking primarily on late endosomes/lysosomes. Upon exposure to the axon guidance cue semaphorin 3A (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 remodeling of subcellular compartments.

PubMed ID: 32073171
PMC ID: PMC7073465
Article link: EMBO J
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: actb ago2 app cd63 dicer1 lamp1 mtor rab5a sema3a thbs1

GEO Series: GSE124168: NCBI

Article Images: [+] show captions
References [+] :
Alami, Axonal transport of TDP-43 mRNA granules is impaired by ALS-causing mutations. 2014, Pubmed