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miR-182 Regulates Slit2-Mediated Axon Guidance by Modulating the Local Translation of a Specific mRNA

Title: miR-182 Regulates Slit2-Mediated Axon Guidance by Modulating the Local Translation of a Specific mRNA
Authors: Bellon, A
Iyer, A
Bridi, S
Lee, FCY
Ovando-Vazquez, C
Corradi, E
Longhi, S
Roccuzzo, M
Strohbuecker, S
Naik, S
Sarkies, P
Miska, E
Abreu-Goodger, C
Holt, CE
Baudet, M-L
Item Type: Journal Article
Abstract: During brain wiring, cue-induced axon behaviors such as directional steering and branching are aided by localized mRNA translation. Different guidance cues elicit translation of subsets of mRNAs that differentially regulate the cytoskeleton, yet little is understood about how specific mRNAs are selected for translation. MicroRNAs (miRNAs) are critical translational regulators that act through a sequence-specific mechanism. Here, we investigate the local role of miRNAs in mRNA-specific translation during pathfinding of Xenopus laevis retinal ganglion cell (RGC) axons. Among a rich repertoire of axonal miRNAs, miR-182 is identified as the most abundant. Loss of miR-182 causes RGC axon targeting defects in vivo and impairs Slit2-induced growth cone (GC) repulsion. We find that miR-182 targets cofilin-1 mRNA, silencing its translation, and Slit2 rapidly relieves the repression without causing miR-182 degradation. Our data support a model whereby miR-182 reversibly gates the selection of transcripts for fast translation depending on the extrinsic cue.
Issue Date: 31-Jan-2017
Date of Acceptance: 27-Dec-2016
URI: http://hdl.handle.net/10044/1/51976
DOI: https://dx.doi.org/10.1016/j.celrep.2016.12.093
ISSN: 2211-1247
Publisher: Elsevier
Start Page: 1171
End Page: 1186
Journal / Book Title: Cell Reports
Volume: 18
Issue: 5
Copyright Statement: This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: Science & Technology
Life Sciences & Biomedicine
Cell Biology
RETINAL GROWTH CONES
PROTEIN-SYNTHESIS
SYMPATHETIC NEURONS
CORTICAL-NEURONS
TARGETING MAP1B
MICRORNAS
XENOPUS
LOCALIZATION
MECHANISMS
EXPRESSION
Slit2
axon guidance
brain wiring
cofilin
growth cone
local translation
miR-182
miRNAs
Publication Status: Published
Appears in Collections:Clinical Sciences
Molecular Sciences
Faculty of Medicine



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