Identification, classification, and expression of RAGE gene splice variants.
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 approximately 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.
Hudson
Barry I
BI
Division of Surgical Science, Department of Surgery, College of Physicians and Surgeons, Columbia University, 630 W. 168th St., PS 17-401, New York, New York 10032, USA. bh2021@columbia.edu
Carter
Angela M
AM
Harja
Evis
E
Kalea
Anastasia Z
AZ
Arriero
Maria
M
Yang
Hojin
H
Grant
Peter J
PJ
Schmidt
Ann Marie
AM
D017398:Alternative Splicing; D001483:Base Sequence; D002478:Cells, Cultured; D003001:Cloning, Molecular; D019295:Computational Biology; D014644:Genetic Variation; D006801:Humans; D008168:Lung / Q000378:metabolism; D008969:Molecular Sequence Data; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D017434:Protein Structure, Tertiary; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000145:classification / Q000235:genetics*
D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic