PUBLICATION

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

Authors
Yergert, K.M., Doll, C.A., O'Rouke, R., Hines, J.H., Appel, B.
ID
ZDB-PUB-210114-17
Date
2021
Source
PLoS Biology   19: e3001053 (Journal)
Registered Authors
Appel, Bruce, Doll, Caleb, Hines, Jacob H.
Keywords
none
MeSH Terms
  • 3' Untranslated Regions/physiology*
  • Animals
  • Animals, Genetically Modified
  • Embryo, Nonmammalian
  • Eukaryotic Initiation Factors/genetics
  • Eukaryotic Initiation Factors/metabolism
  • Molecular Imaging/methods
  • Myelin Sheath/genetics
  • Myelin Sheath/metabolism*
  • RNA Transport/genetics*
  • RNA, Messenger/chemistry
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism*
  • RNA-Binding Proteins/genetics
  • RNA-Binding Proteins/metabolism
  • Regulatory Sequences, Ribonucleic Acid/physiology
  • Sequence Analysis, RNA
  • Tissue Distribution
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
33439856 Full text @ PLoS Biol.
Abstract
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 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. However, the mechanisms by which mRNAs are selectively enriched in myelin sheaths are unclear. To investigate how mRNAs are targeted to myelin sheaths, we tested the hypothesis that transcripts are selected for myelin enrichment through consensus sequences in the 3' untranslated region (3' UTR). Using methods to visualize mRNA in living zebrafish larvae, we identified candidate 3' UTRs that were sufficient to localize mRNA to sheaths and enriched near growth zones of nascent membrane. We bioinformatically identified motifs common in 3' UTRs from 3 myelin-enriched transcripts and determined that these motifs are required and sufficient in a context-dependent manner for mRNA transport to myelin sheaths. Finally, we show that 1 motif is highly enriched in the myelin transcriptome, suggesting that this sequence is a global regulator of mRNA localization during developmental myelination.
Genes / Markers
Figures
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Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes