ESRP1 and ESRP2 are epithelial cell-type-specific regulators of FGFR2 splicing.
Cell-type-specific expression of epithelial and mesenchymal isoforms of Fibroblast Growth Factor Receptor 2 (FGFR2) is achieved through tight regulation of mutually exclusive exons IIIb and IIIc, respectively. Using an application of cell-based cDNA expression screening, we identified two paralogous epithelial cell-type-specific RNA-binding proteins that are essential regulators of FGFR2 splicing. Ectopic expression of either protein in cells that express FGFR2-IIIc caused a switch in endogenous FGFR2 splicing to the epithelial isoform. Conversely, knockdown of both factors in cells that express FGFR2-IIIb by RNA interference caused a switch from the epithelial to mesenchymal isoform. These factors also regulate splicing of CD44, p120-Catenin (CTNND1), and hMena (ENAH), three transcripts that undergo changes in splicing during the epithelial-to-mesenchymal transition (EMT). These studies suggest that Epithelial Splicing Regulatory Proteins 1 and 2 (ESRP1 and ESRP2) are coordinators of an epithelial cell-type-specific splicing program.
Warzecha
Claude C
CC
Department of Medicine, Renal Division, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Sato
Trey K
TK
Nabet
Behnam
B
Hogenesch
John B
JB
Carstens
Russ P
RP
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D051177:Catenins; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism*; D005091:Exons; D005786:Gene Expression Regulation; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D007438:Introns; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000378:metabolism; D020033:Protein Isoforms; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics* / Q000378:metabolism; D014161:Transduction, Genetic; D000095002:Delta Catenin
C497483:CD44 protein, human; D051177:Catenins; D015815:Cell Adhesion Molecules; C539364:ESRP1 protein, human; C539365:ESRP2 protein, human; C511939:Enah protein, human; D018960:Hyaluronan Receptors; D008840:Microfilament Proteins; D010750:Phosphoproteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; C496353:FGFR2 protein, human; C496354:Fgfr2 protein, mouse; D051497:Receptor, Fibroblast Growth Factor, Type 2; D000095002:Delta Catenin