The mouse-specific splice variant mRAGE-v4 encodes a membrane-bound RAGE that is resistant to shedding and does not contribute to the production of soluble RAGE

Stefania Di Maggio, Elena Gatti, Jaron Liu, Matteo Bertolotti, Günter Fritz, Marco E. Bianchi, Angela Raucci

Research output: Contribution to journalArticlepeer-review

Abstract

The receptor for advanced glycation end-products (RAGE) is involved in the onset and progression of several inflammatory diseases. The RAGE primary transcript undergoes numerous alternative splicing (AS) events, some of which are species-specific. Here, we characterize the mouse-specific mRAGE-v4 splice variant, which is conserved in rodents and absent in primates. mRAGE-v4 derives from exon 9 skipping and encodes a receptor (M-RAGE) that lacks 9 amino acids between the transmembrane and the immunoglobulin (Ig) domains. RNA-Seq data confirm that in mouse lung mRAGE-v4 is the most abundant RAGE mRNA isoform after mRAGE, which codes for full-length RAGE (FL-RAGE), while in heart all RAGE variants are almost undetectable. The proteins M-RAGE and FL-RAGE are roughly equally abundant in mouse lung. Contrary to FL-RAGE, M-RAGE is extremely resistant to shedding because it lacks the peptide motif recognized by both ADAM10 and MMP9, and does not contribute significantly to soluble cRAGE formation. Thus, a cassette exon in RAGE corresponds to a specific function of the RAGE protein-the ability to be shed. Given the differences in RAGE AS variants between rodents and humans, caution is due in the interpretation of results obtained in mouse models of RAGE-dependent human pathologies.

Original languageEnglish
Article numbere0153832
JournalPLoS One
Volume11
Issue number9
DOIs
Publication statusPublished - Sep 1 2016

ASJC Scopus subject areas

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

Fingerprint

Dive into the research topics of 'The mouse-specific splice variant mRAGE-v4 encodes a membrane-bound RAGE that is resistant to shedding and does not contribute to the production of soluble RAGE'. Together they form a unique fingerprint.

Cite this