PUBLICATION

RAB13 mRNA compartmentalisation spatially orients tissue morphogenesis

Authors
Costa, G., Bradbury, J.J., Tarannum, N., Herbert, S.P.
ID
ZDB-PUB-201002-93
Date
2020
Source
The EMBO journal   39(21): e106003 (Journal)
Registered Authors
Bradbury, Joshua, Costa, Guilherme, Herbert, Shane
Keywords
angiogenesis, endothelial cell, filopodia, mRNA targeting, zebrafish
Datasets
GEO:GSE155449
MeSH Terms
  • Endothelial Cells/cytology
  • Endothelial Cells/metabolism
  • RNA, Messenger/metabolism*
  • Cell Polarity
  • rab GTP-Binding Proteins/genetics*
  • rab GTP-Binding Proteins/metabolism*
  • Cell Movement
  • Pseudopodia/metabolism
  • Pseudopodia/pathology
  • Animals
  • GTP Phosphohydrolases
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Zebrafish/physiology
  • Gene Editing
  • Morphogenesis/genetics*
  • Morphogenesis/physiology*
(all 17)
PubMed
32946121 Full text @ EMBO J.
Abstract
Polarised targeting of diverse mRNAs to cellular protrusions is a hallmark of cell migration. Although a widespread phenomenon, definitive functions for endogenous targeted mRNAs and their relevance to modulation of in vivo tissue dynamics remain elusive. Here, using single-molecule analysis, gene editing and zebrafish live-cell imaging, we report that mRNA polarisation acts as a molecular compass that orients motile cell polarity and spatially directs tissue movement. Clustering of protrusion-derived RNAseq datasets defined a core 192-nt localisation element underpinning precise mRNA targeting to sites of filopodia formation. Such targeting of the small GTPase RAB13 generated tight spatial coupling of mRNA localisation, translation and protein activity, achieving precise subcellular compartmentalisation of RAB13 protein function to create a polarised domain of filopodia extension. Consequently, genomic excision of this localisation element and perturbation of RAB13 mRNA targeting-but not translation-depolarised filopodia dynamics in motile endothelial cells and induced mispatterning of blood vessels in zebrafish. Hence, mRNA polarisation, not expression, is the primary determinant of the site of RAB13 action, preventing ectopic functionality at inappropriate subcellular loci and orienting tissue morphogenesis.
Genes / Markers
Figures
Figure Gallery (13 images) / 2
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
s843TgTransgenic Insertion
    umc203
      Small Deletion
      umc204TgTransgenic Insertion
        1 - 3 of 3
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        Human Disease / Model
        No data available
        Sequence Targeting Reagents
        Target Reagent Reagent Type
        rab13CRISPR1-rab13CRISPR
        rab13CRISPR2-rab13CRISPR
        1 - 2 of 2
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        Fish
        Antibodies
        No data available
        Orthology
        No data available
        Engineered Foreign Genes
        Marker Marker Type Name
        EGFPEFGEGFP
        GFPEFGGFP
        MCPEFGMCP
        1 - 3 of 3
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        Mapping
        No data available