Identification, classification, and expression ofRAGEgene splice variants

Abstract

The receptor for advanced glycation end-products (RAGE) is a single-transmembrane, mul- tiligand receptor of the immunoglobulin superfamily. RAGE up-regulation is implicated in numerous patho- logical states including vascular disease, diabetes, can- cer, and neurodegeneration. The understanding of the regulation of RAGE is important in both disease patho- genesis 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 reveals50% 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 under- standing of the gene in the normal and pathological state. —Hudson, B. I., Carter, A. M., Harja, E., Kalea, A. Z., Arriero, M., Yang, H., Grant, P. J., Schmidt, A. M. Identification, classification, and expression of RAGE gene splice variants. FASEB J. 22, 1572-1580 (2008)