Axonal precursor miRNAs hitchhike on endosomes and locally regulate the development of neural circuits.
RNA localization
TUBB3
axon
neural circuit development
non-coding RNAs
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
16 03 2020
16 03 2020
Historique:
received:
21
05
2019
revised:
24
12
2019
accepted:
17
01
2020
pubmed:
20
2
2020
medline:
11
11
2020
entrez:
20
2
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32073171
doi: 10.15252/embj.2019102513
pmc: PMC7073465
doi:
Substances chimiques
MicroRNAs
0
RNA Precursors
0
RNA, Untranslated
0
Banques de données
GEO
['GSE124168']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e102513Subventions
Organisme : The Giovanni Armenise-Harvard Foundation
Pays : International
Organisme : Seventh Framework Programme
ID : 618969
Pays : International
Organisme : Ministero dell'Istruzione, dell'Università e della Ricerca (MIUR)
ID : RBSI144NZ4
Pays : International
Organisme : EC | Erasmus+
Pays : International
Organisme : Università degli Studi di Trento (UNITN)
Pays : International
Organisme : Associazione Italiana per la Ricerca sul Cancro (AIRC)
ID : 21315
Pays : International
Organisme : Associazione Italiana per la Ricerca sul Cancro (AIRC)
ID : 20366
Pays : International
Informations de copyright
© 2020 The Authors. Published under the terms of the CC BY NC ND 4.0 license.
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