Axonal precursor miRNAs hitchhike on endosomes and locally regulate the development of neural circuits.

Autor: Corradi, Eloina, Dalla Costa, Irene, Gavoci, Antoneta, Iyer, Archana, Roccuzzo, Michela, Otto, Tegan A, Oliani, Eleonora, Bridi, Simone, Strohbuecker, Stephanie, Santos‐Rodriguez, Gabriela, Valdembri, Donatella, Serini, Guido, Abreu‐Goodger, Cei, Baudet, Marie‐Laure
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Zdroj: EMBO Journal; 3/16/2020, Vol. 39 Issue 6, p1-24, 24p, 1 Diagram, 8 Graphs
Abstrakt: 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. Synopsis: Mechanisms regulating subcellular localization and local function of non‐coding RNA are not well understood. Here, neuronal pre‐miRNAs are found to traffic along axons docked to endosomes, with axonal processing of pre‐miRNAs leading to the inhibition of local protein synthesis. Precursor miRNAs hitchhike onto late endosomes/lysosomes to reach the growth cone.Sema3A, but not Slit2, axon guidance cue induces local biogenesis of specific miRNAs within axons.Newly generated miRNAs inhibit basal translation of TUBB3 but not APP upon Sema3A exposure.miRNAs regulate growth cone steering and the establishment of functional connections. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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