Identification, classification, and expression of RAGE gene splice variants

Barry I. Hudson, Angela M. Carter, Evis Harja, Anastasia Z. Kalea, Maria Arriero, Hojin Yang, Peter J. Grant, Ann Marie Schmidt

Research output: Contribution to journalArticle

242 Scopus citations

Abstract

The receptor for advanced glycation end-products (RAGE) is a single-transmembrane, multiligand receptor of the immunoglobulin superfamily. RAGE up-regulation is implicated in numerous pathological states including vascular disease, diabetes, cancer, and neurodegeneration. The understanding of the regulation of RAGE is important in both disease pathogenesis and normal homeostasis. Here, we demonstrate the characterization and identification of human RAGE splice variants by analysis of RAGE cDNA from tissue and cells. We identified a vast range of splice forms that lead to changes in the protein coding region of RAGE, which we have classified according to the Human Gene Nomenclature Committee (HGNC). These resulted in protein changes in the ligand-binding domain of RAGE or the removal of the transmembrane domain and cytosolic tail. Analysis of splice variants for premature termination codons reveals∼50% of identified variants are targeted to the nonsense-mediated mRNA decay pathway. Expression analysis revealed the RAGE_v1 variant to be the primary secreted soluble isoform of RAGE. Taken together, identification of functional splice variants of RAGE underscores the biological diversity of the RAGE gene and will aid in the understanding of the gene in the normal and pathological state.

Original languageEnglish (US)
Pages (from-to)1572-1580
Number of pages9
JournalFASEB Journal
Volume22
Issue number5
DOIs
StatePublished - May 1 2008
Externally publishedYes

Keywords

  • DNA cloning
  • RNA splicing

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

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  • Cite this

    Hudson, B. I., Carter, A. M., Harja, E., Kalea, A. Z., Arriero, M., Yang, H., Grant, P. J., & Schmidt, A. M. (2008). Identification, classification, and expression of RAGE gene splice variants. FASEB Journal, 22(5), 1572-1580. https://doi.org/10.1096/fj.07-9909com