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

Publication date: 31 January 2017
Source:Cell Reports, Volume 18, Issue 5
Author(s): 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
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

Teaser

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.


http://ift.tt/2kMP1JJ


http://ift.tt/2jRHSJV