miR-182 Regulates Slit2-Mediated Axon Guidance by Modulating the Local Translation of a Specific mRNA
| Autor: | Bellon A, Iyer A, Bridi S, Flora Lee, Ovando-Vázquez C, Corradi E, Longhi S, Roccuzzo M, Strohbuecker S, Naik S, Sarkies P, Miska E, Abreu-Goodger C, Ce, Holt, Ml, Baudet |
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| Přispěvatelé: | Miska, Eric [0000-0002-4450-576X], Holt, Christine [0000-0003-2829-121X], Apollo - University of Cambridge Repository |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Genetics and Molecular Biology (all)
Retinal Ganglion Cells EXPRESSION MICRORNAS Growth Cones Nerve Tissue Proteins cofilin Biochemistry Article MECHANISMS Xenopus laevis local translation brain wiring Slit2 Animals RNA Messenger lcsh:QH301-705.5 TARGETING MAP1B Science & Technology axon guidance CORTICAL-NEURONS LOCALIZATION Cell Biology growth cone miR-182 miRNAs Biochemistry Genetics and Molecular Biology (all) Axons SYMPATHETIC NEURONS XENOPUS lcsh:Biology (General) Gene Expression Regulation Protein Biosynthesis PROTEIN-SYNTHESIS Intercellular Signaling Peptides and Proteins RETINAL GROWTH CONES Life Sciences & Biomedicine |
| Zdroj: | 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, vol. 18, no. 5, pp. 1171-1186 . https://doi.org/10.1016/j.celrep.2016.12.093 Cell Reports Europe PubMed Central Cell Reports, Vol 18, Iss 5, Pp 1171-1186 (2017) |
| DOI: | 10.1016/j.celrep.2016.12.093 |
| Popis: | Summary 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. Graphical Abstract Highlights • Small RNA-seq analysis reveals that miR-182 is the most abundant miRNA in RGC axons • miR-182 regulates Slit2-mediated axon guidance of RGCs in vitro and in vivo • miR-182 silences cofilin-1 local protein synthesis in growth cones • Slit2 rapidly lifts miR-182-mediated repression of cofilin-1 without degrading it Bellon et al. examine how specific mRNAs are selected for cue-induced local protein synthesis during axon guidance and find that miR-182 reversibly regulates the selective translation of a specific transcript to facilitate fast growth cone steering and axon guidance. |
| Databáze: | OpenAIRE |
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