Efficient use of a 'dead-end' GA 5' splice site in the human fibroblast growth factor receptor genes

EMBO J. 2003 Apr 1;22(7):1620-31. doi: 10.1093/emboj/cdg163.


We have investigated use of a conserved non-canonical GA 5' splice site present in vertebrate fibroblast growth factor receptor (FGFR) genes. Despite previous studies suggesting that GA at the beginning of an intron is incompatible with splicing, we observe efficient utilization of this splice site for human FGFR1 gene constructs. We show that use of the GA splice site is dependent on both a conventional splice site six nucleotides upstream and sequence elements within the downstream intron. Furthermore, our results are consistent with competition between the tandem 5' splice sites being mediated by U6 snRNP, rather than U1 snRNP. Thus the GA 5' splice site represents an extension of the adjacent conventional 5' splice site, the first natural example of such a composite 5' splice site.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing*
  • Animals
  • Base Sequence
  • Cell Line
  • DNA
  • Exons
  • Humans
  • Introns
  • Molecular Sequence Data
  • Mutagenesis
  • Receptors, Fibroblast Growth Factor / genetics*
  • Regulatory Sequences, Nucleic Acid
  • Reverse Transcriptase Polymerase Chain Reaction
  • Ribonucleoprotein, U1 Small Nuclear / physiology*
  • Ribonucleoprotein, U4-U6 Small Nuclear / physiology*
  • Sequence Homology, Nucleic Acid


  • Receptors, Fibroblast Growth Factor
  • Ribonucleoprotein, U1 Small Nuclear
  • Ribonucleoprotein, U4-U6 Small Nuclear
  • DNA