ESRP1 and ESRP2 are epithelial cell-type-specific regulators of FGFR2 splicing

Mol Cell. 2009 Mar 13;33(5):591-601. doi: 10.1016/j.molcel.2009.01.025.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing*
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Catenins
  • Cell Adhesion Molecules / metabolism
  • Cell Line
  • Epithelial Cells / metabolism*
  • Exons
  • Gene Expression Regulation
  • Humans
  • Hyaluronan Receptors / metabolism
  • Introns
  • Mice
  • Mice, Inbred C57BL
  • Microfilament Proteins / metabolism
  • Molecular Sequence Data
  • Phosphoproteins / metabolism
  • Protein Isoforms
  • RNA Interference
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Receptor, Fibroblast Growth Factor, Type 2 / genetics*
  • Receptor, Fibroblast Growth Factor, Type 2 / metabolism
  • Transduction, Genetic

Substances

  • CD44 protein, human
  • Catenins
  • Cell Adhesion Molecules
  • ESRP1 protein, human
  • ESRP2 protein, human
  • Enah protein, human
  • Hyaluronan Receptors
  • Microfilament Proteins
  • Phosphoproteins
  • Protein Isoforms
  • RNA, Messenger
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • delta catenin
  • FGFR2 protein, human
  • Fgfr2 protein, mouse
  • Receptor, Fibroblast Growth Factor, Type 2