Identification of a classic nuclear localization signal at the N terminus that regulates the subcellular localization of Rbfox2 isoforms during differentiation of NMuMG and P19 cells

FEBS Lett. 2016 Dec;590(24):4453-4460. doi: 10.1002/1873-3468.12492. Epub 2016 Dec 1.

Abstract

Nuclear localization of the alternative splicing factor Rbfox2 is achieved by a C-terminal nuclear localization signal (NLS) which can be excluded from some Rbfox2 isoforms by alternative splicing. While this predicts nuclear and cytoplasmic localization, Rbfox2 is exclusively nuclear in some cell types. Here, we identify a second NLS in the N terminus of Rbfox2 isoform 1A that is not included in Rbfox2 isoform 1F. Rbfox2 1A isoforms lacking the C-terminal NLS are nuclear, whereas equivalent 1F isoforms are cytoplasmic. A shift in Rbfox2 expression toward cytoplasmic 1F isoforms occurs during epithelial to mesenchymal transition (EMT) and could be important in regulating the activity and function of Rbfox2.

Keywords: NLS; Rbfox; Rbfox2; cytoplasmic; nuclear; splicing.

Publication types

  • Letter

MeSH terms

  • Alternative Splicing*
  • Amino Acid Sequence
  • Animals
  • Cell Differentiation / drug effects
  • Cell Line
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Cytoplasm / metabolism
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism*
  • Epithelial-Mesenchymal Transition / genetics*
  • Mammary Glands, Animal / cytology
  • Mammary Glands, Animal / drug effects
  • Mammary Glands, Animal / metabolism
  • Mice
  • Mouse Embryonic Stem Cells / cytology
  • Mouse Embryonic Stem Cells / drug effects
  • Mouse Embryonic Stem Cells / metabolism*
  • Nuclear Localization Signals / chemistry
  • Nuclear Localization Signals / genetics*
  • Nuclear Localization Signals / metabolism
  • Protein Domains
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • RNA Splicing Factors / chemistry
  • RNA Splicing Factors / genetics*
  • RNA Splicing Factors / metabolism
  • Sequence Alignment
  • Signal Transduction
  • Transforming Growth Factor beta1 / pharmacology

Substances

  • Nuclear Localization Signals
  • Protein Isoforms
  • RNA Splicing Factors
  • Rbfox2 protein, mouse
  • Transforming Growth Factor beta1