miR-182 regulates Slit2-mediated axon guidance by modulating the local translation of a specific mRNA

Anaïs Bellon; Archana Iyer; Simone Bridi; Flora C.Y. Lee; Cesaré Ovando-Vázquez; Eloina Corradi; Sara Longhi; Michela Roccuzzo; Stephanie Strohbuecker; Sindhu Naik; Peter Sarkies; Eric Miska; Cei Abreu-Goodger; Christine E. Holt; Marie-Laure Baudet

doi:10.1016/j.celrep.2016.12.093

miR-182 regulates Slit2-mediated axon guidance by modulating the local translation of a specific mRNA

Anaïs Bellon, Archana Iyer, Simone Bridi, Flora C.Y. Lee, Cesaré Ovando-Vázquez, Eloina Corradi, Sara Longhi, Michela Roccuzzo, Stephanie Strohbuecker, Sindhu Naik, Peter Sarkies, Eric Miska, Cei Abreu-Goodger, Christine E. Holt, Marie-Laure Baudet

School of Biological Sciences

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	1171-1186
Number of pages	16
Journal	Cell Reports
Volume	18
Issue number	5
DOIs	https://doi.org/10.1016/j.celrep.2016.12.093
Publication status	Published - 31 Jan 2017

Keywords / Materials (for Non-textual outputs)

miRNAs
local translation
growth cone
axon guidance
brain wiring
miR-182
Slit2
cofilin

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10.1016/j.celrep.2016.12.093Licence: Creative Commons: Attribution (CC-BY)

BaudetETal2017miR-182RegulatesSlit2MediatedAxonFinal published version, 16 MBLicence: Creative Commons: Attribution (CC-BY)

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Bellon, A., Iyer, A., Bridi, S., Lee, F. C. Y., Ovando-Vázquez, C., Corradi, E., Longhi, S., Roccuzzo, M., Strohbuecker, S., Naik, S., Sarkies, P., Miska, E., Abreu-Goodger, C., Holt, C. E., & Baudet, M.-L. (2017). miR-182 regulates Slit2-mediated axon guidance by modulating the local translation of a specific mRNA. Cell Reports, 18(5), 1171-1186. https://doi.org/10.1016/j.celrep.2016.12.093

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title = "miR-182 regulates Slit2-mediated axon guidance by modulating the local translation of a specific mRNA",

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.",

keywords = "miRNAs, local translation, growth cone, axon guidance, brain wiring, miR-182, Slit2, cofilin",

author = "Ana{\"i}s Bellon and Archana Iyer and Simone Bridi and Lee, \{Flora C.Y.\} and Cesar{\'e} Ovando-V{\'a}zquez and Eloina Corradi and Sara Longhi and Michela Roccuzzo and Stephanie Strohbuecker and Sindhu Naik and Peter Sarkies and Eric Miska and Cei Abreu-Goodger and Holt, \{Christine E.\} and Marie-Laure Baudet",

year = "2017",

month = jan,

day = "31",

doi = "10.1016/j.celrep.2016.12.093",

language = "English",

volume = "18",

pages = "1171--1186",

journal = "Cell Reports",

issn = "2211-1247",

publisher = "Cell Press",

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Bellon, A, Iyer, A, Bridi, S, Lee, FCY, Ovando-Vázquez, C, Corradi, E, Longhi, S, Roccuzzo, M, Strohbuecker, S, Naik, S, Sarkies, P, Miska, E, Abreu-Goodger, C, Holt, CE & Baudet, M-L 2017, 'miR-182 regulates Slit2-mediated axon guidance by modulating the local translation of a specific mRNA', Cell Reports, vol. 18, no. 5, pp. 1171-1186. https://doi.org/10.1016/j.celrep.2016.12.093

TY - JOUR

T1 - miR-182 regulates Slit2-mediated axon guidance by modulating the local translation of a specific mRNA

AU - Bellon, Anaïs

AU - Iyer, Archana

AU - Bridi, Simone

AU - Lee, Flora C.Y.

AU - Ovando-Vázquez, Cesaré

AU - Corradi, Eloina

AU - Longhi, Sara

AU - Roccuzzo, Michela

AU - Strohbuecker, Stephanie

AU - Naik, Sindhu

AU - Sarkies, Peter

AU - Miska, Eric

AU - Abreu-Goodger, Cei

AU - Holt, Christine E.

AU - Baudet, Marie-Laure

PY - 2017/1/31

Y1 - 2017/1/31

N2 - 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.

AB - 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.

KW - miRNAs

KW - local translation

KW - growth cone

KW - axon guidance

KW - brain wiring

KW - miR-182

KW - Slit2

KW - cofilin

U2 - 10.1016/j.celrep.2016.12.093

DO - 10.1016/j.celrep.2016.12.093

M3 - Article

SN - 2211-1247

VL - 18

SP - 1171

EP - 1186

JO - Cell Reports

JF - Cell Reports

IS - 5

ER -

miR-182 regulates Slit2-mediated axon guidance by modulating the local translation of a specific mRNA

Abstract

Keywords / Materials (for Non-textual outputs)

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