An ESRP-regulated splicing programme is abrogated during the epithelial-mesenchymal transition.
Alternative splicing achieves coordinated changes in post-transcriptional gene expression programmes through the activities of diverse RNA-binding proteins. Epithelial splicing regulatory proteins 1 and 2 (ESRP1 and ESRP2) are cell-type-specific regulators of transcripts that switch splicing during the epithelial-mesenchymal transition (EMT). To define a comprehensive programme of alternative splicing that is regulated during the EMT, we identified an extensive ESRP-regulated splicing network of hundreds of alternative splicing events within numerous genes with functions in cell-cell adhesion, polarity, and migration. Loss of this global ESRP-regulated epithelial splicing programme induces the phenotypic changes in cell morphology that are observed during the EMT. Components of this splicing signature provide novel molecular markers that can be used to characterize the EMT. Bioinformatics and experimental approaches revealed a high-affinity ESRP-binding motif and a predictive RNA map that governs their activity. This work establishes the ESRPs as coordinators of a complex alternative splicing network that adds an important post-transcriptional layer to the changes in gene expression that underlie epithelial-mesenchymal transitions during development and disease.
Warzecha
Claude C
CC
Renal Division, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Jiang
Peng
P
Amirikian
Karine
K
Dittmar
Kimberly A
KA
Lu
Hezhe
H
Shen
Shihao
S
Guo
Wei
W
Xing
Yi
Y
Carstens
Russ P
RP
D017398:Alternative Splicing / Q000502:physiology*; D001665:Binding Sites / Q000235:genetics; D002448:Cell Adhesion / Q000235:genetics; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics; D016764:Cell Polarity / Q000235:genetics; D019295:Computational Biology; D024202:Electrophoretic Mobility Shift Assay; D004847:Epithelial Cells / Q000166:cytology*; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D008648:Mesoderm / Q000166:cytology*; D046228:Microarray Analysis; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D033921:Vesicular Transport Proteins / Q000235:genetics
C539364:ESRP1 protein, human; C539365:ESRP2 protein, human; D016601:RNA-Binding Proteins; D033921:Vesicular Transport Proteins