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Identification of 3′ UTR motifs required for mRNA localization to myelin sheaths in vivo

Myelin is a specialized membrane produced by oligodendrocytes that insulates and supports axons. Oligodendrocytes extend numerous cellular processes, as projections of the plasma membrane, and simultaneously wrap multiple layers of myelin membrane around target axons. Notably, myelin sheaths originating from the same oligodendrocyte are variable in size, suggesting that local mechanisms regulate myelin sheath growth. Purified myelin contains ribosomes and hundreds of mRNAs, supporting a model that mRNA localization and local protein synthesis regulate sheath growth and maturation, but the mechanisms by which mRNAs are selectively enriched in myelin sheaths are unclear. Yergert et al. tested the hypothesis that transcripts are selected for myelin enrichment through consensus sequences in the 3′ untranslated region (3′ UTR). Visualizing mRNA in living zebrafish larvae, they identified candidate 3′ UTRs that were sufficient to localize mRNA to sheaths and enriched near growth zones of nascent membrane. They also bioinformatically identified motifs common to several myelin-enriched transcripts, finding that these motifs are necessary and sufficient in a context-dependent manner for mRNA transport to myelin sheaths, and that one such motif is highly enriched in the myelin transcriptome, suggesting that it is a global regulator of mRNA localization during developmental myelination. The image shows staining of mbpa mRNA in the hindbrain of 4-day post-fertilization transgenic zebrafish larvae. Individual mbpa transcripts are visualized in magenta/yellow, oligodendrocytes and myelin tracts are labeled with EGFP-CAAX (green), and nuclei are stained with DAPI (blue).

Image Credit: Katie Yergert

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