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
-
- Gene Editing
- Animals
- Cell Polarity
- rab GTP-Binding Proteins/genetics*
- rab GTP-Binding Proteins/metabolism*
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish/physiology
- Pseudopodia/metabolism
- Pseudopodia/pathology
- GTP Phosphohydrolases
- Morphogenesis/genetics*
- Morphogenesis/physiology*
- RNA, Messenger/metabolism*
- Cell Movement
- Endothelial Cells/cytology
- Endothelial Cells/metabolism
- PubMed
- 32946121 Full text @ EMBO J.
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.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping