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
Show all Figures
Expression
Gene Antibody Fish Conditions Stage Qualifier Anatomy Assay Figure
EGFPumc204Tgstandard conditionsPrim-5IFL
EGFPumc204Tgstandard conditionsPrim-5IFL
rab13rab13umc203/+standard conditionsPrim-5RTPCR
rab13rab13umc203/umc203standard conditionsPrim-5RTPCR
rab13WTstandard conditionsPrim-5RTPCR
1 - 5 of 5
Show
Phenotype
Fish Conditions Stage Phenotype Figure
rab13umc203/umc203; s843Tgstandard conditionsPrim-5
rab13umc203/umc203; s843Tgstandard conditionsPrim-5
1 - 2 of 2
Show
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
s843TgTransgenic Insertion
    umc203
      		Small Deletion
      umc204TgTransgenic Insertion
        1 - 3 of 3
        Show
        Human Disease / Model
        No data available
        Sequence Targeting Reagents
        Target Reagent Reagent Type
        rab13CRISPR1-rab13CRISPR
        rab13CRISPR2-rab13CRISPR
        1 - 2 of 2
        Show
        Fish
        Fish
        rab13umc203/+
        rab13umc203/umc203
        rab13umc203/umc203; s843Tg
        umc204Tg
        WT
        1 - 5 of 5
        Show
        Antibodies
        No data available
        Orthology
        No data available
        Engineered Foreign Genes
        Marker Marker Type Name
        EGFPEFGEGFP
        GFPEFGGFP
        MCPEFGMCP
        1 - 3 of 3
        Show
        Mapping
        No data available
        Your Input Welcome
        We welcome your input and comments. Please use this form to recommend updates to the information in ZFIN. We appreciate as much detail as possible and references as appropriate. We will review your comments promptly.
        Citation
        Costa, G., Bradbury, J.J., Tarannum, N., Herbert, S.P. (2020) RAB13 mRNA compartmentalisation spatially orients tissue morphogenesis. The EMBO journal. 39(21):e106003.