XB-ART-53046
Cell Rep
January 1, 2017;
18
(5):
1171-1186.
miR-182 Regulates Slit2-Mediated Axon Guidance by Modulating the Local Translation of a Specific mRNA.
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 ML
.
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.
PubMed ID: 28147273
PMC ID: PMC5300892
Article link: Cell Rep
Grant support: [+]
085314/Z/08/Z Wellcome Trust
Species referenced: Xenopus laevis
Genes referenced: actr2 bdnf cfl1 gnl3 map2 mmut nrp1 ntn1 pdk4 prl.2 rgs19 rhoa sema3a slit2 ugcg
Morpholinos: miR-182 MO1 slit2 MO4 slit2 MO5
GEO Series: GSE86883: NCBI
Article Images: [+] show captions
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Baudet, miR-124 acts through CoREST to control onset of Sema3A sensitivity in navigating retinal growth cones. 2011, Pubmed , Xenbase
Bazzini, Ribosome profiling shows that miR-430 reduces translation before causing mRNA decay in zebrafish. 2012, Pubmed
Bouquet, Molecular mechanisms of axonal growth. 2008, Pubmed
Brittis, Axonal protein synthesis provides a mechanism for localized regulation at an intermediate target. 2002, Pubmed
Campbell, Chemotropic responses of retinal growth cones mediated by rapid local protein synthesis and degradation. 2001, Pubmed , Xenbase
Cornel, Precocious pathfinding: retinal axons can navigate in an axonless brain. 1993, Pubmed , Xenbase
Dajas-Bailador, microRNA-9 regulates axon extension and branching by targeting Map1b in mouse cortical neurons. 2012, Pubmed , Xenbase
De Pietri Tonelli, Single-cell detection of microRNAs in developing vertebrate embryos after acute administration of a dual-fluorescence reporter/sensor plasmid. 2006, Pubmed
Deglincerti, Insights into the roles of local translation from the axonal transcriptome. 2012, Pubmed
Djuranovic, miRNA-mediated gene silencing by translational repression followed by mRNA deadenylation and decay. 2012, Pubmed
Eichhorn, mRNA destabilization is the dominant effect of mammalian microRNAs by the time substantial repression ensues. 2014, Pubmed
Erskine, Retinal ganglion cell axon guidance in the mouse optic chiasm: expression and function of robos and slits. 2000, Pubmed
Falk, Electroporation of cDNA/Morpholinos to targeted areas of embryonic CNS in Xenopus. 2007, Pubmed , Xenbase
Gardiner, Competing Interactions of RNA-Binding Proteins, MicroRNAs, and Their Targets Control Neuronal Development and Function. 2015, Pubmed
Gumy, New insights into mRNA trafficking in axons. 2014, Pubmed
Gumy, Transcriptome analysis of embryonic and adult sensory axons reveals changes in mRNA repertoire localization. 2010, Pubmed
Han, Regulation of chemotropic guidance of nerve growth cones by microRNA. 2011, Pubmed , Xenbase
Hancock, MicroRNA-132 is enriched in developing axons, locally regulates Rasa1 mRNA, and promotes axon extension. 2014, Pubmed
Hengst, Functional and selective RNA interference in developing axons and growth cones. 2006, Pubmed
Hocking, Distinct roles for Robo2 in the regulation of axon and dendrite growth by retinal ganglion cells. 2010, Pubmed , Xenbase
Holt, The central dogma decentralized: new perspectives on RNA function and local translation in neurons. 2013, Pubmed
Holt, A single-cell analysis of early retinal ganglion cell differentiation in Xenopus: from soma to axon tip. 1989, Pubmed , Xenbase
Iyer, microRNAs in axon guidance. 2014, Pubmed
Kar, Intra-axonal synthesis of eukaryotic translation initiation factors regulates local protein synthesis and axon growth in rat sympathetic neurons. 2013, Pubmed
Kim, Biogenesis of small RNAs in animals. 2009, Pubmed
Kleiman, Differential subcellular localization of particular mRNAs in hippocampal neurons in culture. 1991, Pubmed
Krol, The widespread regulation of microRNA biogenesis, function and decay. 2010, Pubmed
Krol, Characterizing light-regulated retinal microRNAs reveals rapid turnover as a common property of neuronal microRNAs. 2010, Pubmed
Leung, Live visualization of protein synthesis in axonal growth cones by microinjection of photoconvertible Kaede into Xenopus embryos. 2008, Pubmed , Xenbase
Leung, Asymmetrical beta-actin mRNA translation in growth cones mediates attractive turning to netrin-1. 2006, Pubmed , Xenbase
Lin, Local translation and directional steering in axons. 2007, Pubmed
Lohof, Asymmetric modulation of cytosolic cAMP activity induces growth cone turning. 1992, Pubmed , Xenbase
Natera-Naranjo, Identification and quantitative analyses of microRNAs located in the distal axons of sympathetic neurons. 2010, Pubmed
Nguyen-Ba-Charvet, Sensory axon response to substrate-bound Slit2 is modulated by laminin and cyclic GMP. 2001, Pubmed
Obernosterer, Locked nucleic acid-based in situ detection of microRNAs in mouse tissue sections. 2007, Pubmed
Ovando-Vázquez, Improving microRNA target prediction with gene expression profiles. 2016, Pubmed
Pinter, Perturbations of microRNA function in mouse dicer mutants produce retinal defects and lead to aberrant axon pathfinding at the optic chiasm. 2010, Pubmed
Piper, NF-protocadherin and TAF1 regulate retinal axon initiation and elongation in vivo. 2008, Pubmed , Xenbase
Piper, Signaling mechanisms underlying Slit2-induced collapse of Xenopus retinal growth cones. 2006, Pubmed , Xenbase
Rüegger, MicroRNA turnover: when, how, and why. 2012, Pubmed
Sasaki, Identification of axon-enriched microRNAs localized to growth cones of cortical neurons. 2014, Pubmed
Schmittgen, Analyzing real-time PCR data by the comparative C(T) method. 2008, Pubmed
Schratt, A brain-specific microRNA regulates dendritic spine development. 2006, Pubmed
Shigeoka, Cell biology in neuroscience: RNA-based mechanisms underlying axon guidance. 2013, Pubmed
Tcherkezian, Transmembrane receptor DCC associates with protein synthesis machinery and regulates translation. 2010, Pubmed
Vuppalanchi, Regulation of mRNA transport and translation in axons. 2009, Pubmed
Walz, Chondroitin sulfate disrupts axon pathfinding in the optic tract and alters growth cone dynamics. 2002, Pubmed , Xenbase
Wang, FMRP-Mediated Axonal Delivery of miR-181d Regulates Axon Elongation by Locally Targeting Map1b and Calm1. 2016, Pubmed
Wei, Roles of miR-182 in sensory organ development and cancer. 2015, Pubmed
Wienholds, MicroRNA expression in zebrafish embryonic development. 2005, Pubmed
Wu, Local translation of RhoA regulates growth cone collapse. 2005, Pubmed
Yao, An essential role for beta-actin mRNA localization and translation in Ca2+-dependent growth cone guidance. 2006, Pubmed , Xenbase
Yoon, Local translation of extranuclear lamin B promotes axon maintenance. 2012, Pubmed , Xenbase
Zelina, Signaling switch of the axon guidance receptor Robo3 during vertebrate evolution. 2014, Pubmed
Zhang, The MicroRNA-17-92 cluster enhances axonal outgrowth in embryonic cortical neurons. 2013, Pubmed
Zivraj, Subcellular profiling reveals distinct and developmentally regulated repertoire of growth cone mRNAs. 2010, Pubmed , Xenbase